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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Spinocerebellar Ataxia Type 11 - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Spinocerebellar Ataxia Type 11">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2019/10/31">
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<meta name="citation_author" content="Zhongbo Chen">
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<meta name="citation_author" content="Arina Puzriakova">
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<meta name="citation_author" content="Henry Houlden">
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<meta name="citation_keywords" content="SCA11">
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<meta name="citation_keywords" content="SCA11">
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<meta name="citation_keywords" content="Tau-tubulin kinase 2">
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<meta name="citation_keywords" content="TTBK2">
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<meta name="citation_keywords" content="Spinocerebellar Ataxia Type 11">
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<meta name="DC.Title" content="Spinocerebellar Ataxia Type 11">
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<meta name="DC.Contributor" content="Zhongbo Chen">
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<meta name="DC.Contributor" content="Arina Puzriakova">
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<meta name="DC.Contributor" content="Henry Houlden">
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<meta name="description" content="Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia and abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus). Pyramidal features are seen on occasion. Peripheral neuropathy and dystonia are rare. Six families have been reported to date, one each from the UK, Pakistan, France, Germany, Denmark, and China. Age of onset ranged from early childhood to the mid-40s. Life span is thought to be normal.">
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<meta name="og:description" content="Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia and abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus). Pyramidal features are seen on occasion. Peripheral neuropathy and dystonia are rare. Six families have been reported to date, one each from the UK, Pakistan, France, Germany, Denmark, and China. Age of onset ranged from early childhood to the mid-40s. Life span is thought to be normal.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1757_"><span class="title" itemprop="name">Spinocerebellar Ataxia Type 11</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: SCA11</div><p class="contribs">Chen Z, Puzriakova A, Houlden H.</p><p class="fm-aai"><a href="#_NBK1757_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 17 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="sca11.Summary" itemprop="description"><h2 id="_sca11_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia and abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus). Pyramidal features are seen on occasion. Peripheral neuropathy and dystonia are rare. Six families have been reported to date, one each from the UK, Pakistan, France, Germany, Denmark, and China. Age of onset ranged from early childhood to the mid-40s. Life span is thought to be normal.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of spinocerebellar ataxia type 11 (SCA11) is established in a proband with a heterozygous pathogenic variant in <i>TTBK2</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management is supportive; there are no known disease-modifying treatments to date. Physiotherapy and assessment for assistive devices for ambulation; occupational therapy, including home adaptations; speech and language therapy for dysarthria and dysphagia; ankle-foot orthotics if required and good foot care for those with neuropathy; treatment per ophthalmologist for vision issues; prism glasses may be helpful for diplopia.</p><p><i>Surveillance:</i> Annual neurologic evaluation; evaluations with physiotherapist, occupational therapist, speech and language therapist, and ophthalmologist as indicated.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>SCA11 is inherited in an autosomal dominant manner. The proportion of SCA11 caused by <i>de novo</i> mutation is unknown. Each child of an individual with SCA11 has a 50% chance of inheriting the pathogenic variant. Prenatal testing for an at-risk pregnancy is possible if the diagnosis has been established by molecular genetic testing in an affected family member.</p></div></div><div id="sca11.Diagnosis"><h2 id="_sca11_Diagnosis_">Diagnosis</h2><div id="sca11.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Spinocerebellar ataxia type 11 (SCA11) <b>should be considered</b> in individuals with the following clinical features:</p><ul><li class="half_rhythm"><div>Progressive cerebellar ataxia</div></li><li class="half_rhythm"><div>Abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus)</div></li><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Pyramidal features (mild-to-moderate lower-extremity hyperreflexia; in very rare cases, a positive Babinski sign or other pyramidal features)</div></li><li class="half_rhythm"><div>Swallowing difficulties</div></li></ul><p>Rare findings in SCA11:</p><ul><li class="half_rhythm"><div>Peripheral neuropathy</div></li><li class="half_rhythm"><div>Dystonia</div></li></ul></div><div id="sca11.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of spinocerebellar ataxia type 11 (SCA11) <b>is established</b> in a proband with a heterozygous pathogenic variant in <i>TTBK2</i> identified by molecular genetic testing (see <a href="/books/NBK1757/table/sca11.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobsca11Tmoleculargenetictestingusedi">Table 1</a>).</p><p>Because the phenotype of SCA11 is indistinguishable from many other inherited disorders with ataxia, recommended molecular genetic testing approaches include use of a <b>multigene panel</b> or <b>comprehensive genomic testing</b>.</p><p>Note: Single-gene testing (sequence analysis of <i>TTBK2</i>, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>An ataxia</b>
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<b>multigene panel</b> that includes <i>TTBK2</i> and other genes of interest (see <a href="#sca11.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. Of note, given the rarity of SCA11, some panels for ataxia may not include this gene. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is another good option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Tmoleculargenetictestingusedi"><a href="/books/NBK1757/table/sca11.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobsca11Tmoleculargenetictestingusedi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.molecular_genetic_testing_used_i"><a href="/books/NBK1757/table/sca11.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobsca11Tmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Spinocerebellar Ataxia Type 11 </p></div></div></div></div><div id="sca11.Clinical_Characteristics"><h2 id="_sca11_Clinical_Characteristics_">Clinical Characteristics</h2><div id="sca11.Clinical_Description"><h3>Clinical Description</h3><p>To date, 28 individuals from six families have been identified with a pathogenic variant in <i>TTBK2</i> [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>, <a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>, <a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>, <a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al 2020</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Tclinicalfeaturesofspinocerebe"><a href="/books/NBK1757/table/sca11.T.clinical_features_of_spinocerebe/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobsca11Tclinicalfeaturesofspinocerebe"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.clinical_features_of_spinocerebe"><a href="/books/NBK1757/table/sca11.T.clinical_features_of_spinocerebe/?report=objectonly" target="object" rid-ob="figobsca11Tclinicalfeaturesofspinocerebe">Table 2. </a></h4><p class="float-caption no_bottom_margin">Clinical Features of Spinocerebellar Ataxia Type 11 </p></div></div><p><b>Onset.</b> In the six families described with spinocerebellar ataxia type 11 (SCA11), age of onset ranged from age nine years in the family of Danish origin to age 40-50 years in the families from France, Germany, and China. Most individuals present with a pure ataxia phenotype, with few additional features. Abnormal eye findings were identified in a third of individuals, a small proportion of whom presented with diplopia at onset.</p><p><b>Ataxia.</b> The cerebellar ataxia was clinically similar in all six families. All individuals presented with an ataxia-predominant disorder and difficulty walking due to unsteadiness and maintaining balance. In approximately a third of individuals, limb ataxia was also present. Ataxia was usually slowly progressive. For example, in the British family described, the mean disease duration was 26.8 years [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>].</p><p><b>Abnormal eye findings</b> include jerky pursuit and horizontal and vertical nystagmus. All of the individuals with SCA11 from Devon had abnormal eye movements at presentation, with jerky pursuit and vertical nystagmus more prevalent than horizontal nystagmus [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. Half of the individuals with vertical nystagmus had an upbeat nystagmus [<a class="bibr" href="#sca11.REF.giunti.2012" rid="sca11.REF.giunti.2012">Giunti et al 2012</a>]. Only a very small proportion were found to be symptomatic with ophthalmoplegia and diplopia. No members of the French family had abnormal eye findings. One individual in the German family had oculomotor disturbances with jerky pursuit, gaze-evoked nystagmus, dysmetric saccades, and impaired optokinetic nystagmus on presentation, nine years after symptom onset [<a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>]. In the Danish family, one individual presented with diplopia and nystagmus at age nine years [<a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>]. A sib presented at age four years with ataxia and was found to have nystagmus at age nine years [<a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>]. Three individuals of Chinese descent had nystagmus at the time of presentation [<a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al 2020</a>]. It is unclear if abnormal eye findings progress, but ocular symptoms were the only presenting feature for one individual out of 28 affected. Although abnormal eye findings may be seen at the time of presentation, they are rarely symptomatic.</p><p><b>Pyramidal features</b> exist in varying degrees across the different families. In the British family, mild limb hyperreflexia more prevalent in the upper than the lower limbs (with negative Babinski sign) was found in all but one affected individual [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. In the family from Pakistan, mild-to-moderate hyperreflexia was observed in only two of five affected individuals [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. Only one of the three individuals affected from the Danish family had hyperreflexia [<a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>]. Two of the five individuals of Chinese descent had hyperreflexia [<a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al 2020</a>]. Reflexes and tone were, however, normal in the German and French families described [<a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>].</p><p>No other pyramidal signs apart from hyperreflexia were observed in the 28 individuals apart from one individual with upgoing plantar reflexes. This individual from Devon presented with both extrapyramidal and pyramidal signs including spastic gait, hyperreflexia with upgoing plantar reflexes, "no-no" head tremor, and upper-limb tremor with laterocollis [<a class="bibr" href="#sca11.REF.giunti.2012" rid="sca11.REF.giunti.2012">Giunti et al 2012</a>]. No extrapyramidal signs have been described in other individuals.</p><p><b>Bulbar symptoms.</b> Dysarthria and swallowing difficulties are common in individuals with SCA11. Dysarthria as a result of cerebellar dysfunction was moderate to severe in almost all individuals in the families of British and Pakistani origin but was not present at diagnosis [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. In the French family, dysarthria was an early feature [<a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>]. Dysarthria was reported to be progressive in individuals in the family of Chinese origin [<a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al 2020</a>]. Liquid dysphagia was also noted in individuals with SCA11, especially in the families from Devon and China, but was not common at presentation.</p><p><b>Peripheral neuropathy</b> is not a common feature of SCA11. In the British cohort, nerve conduction studies (NCS) and electromyography (EMG) were normal in eight affected subjects [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. One other affected subject had slightly small sensory nerve action potentials at the age of 61 (disease duration 43 years) but without clinically manifesting neuropathy. In the Pakistani, Danish, French, and German families, neuropathy was not seen. In the Chinese family, EMG of the proband showed extensive neurogenic damage. Somatosensory evoked potentials of the lower limbs were abnormal. Generalized neurogenic damage was seen on NCS and EMG of two other affected Chinese individuals, but it is not apparent whether these individuals also presented with neuropathy symptoms clinically.</p><p><b>Other.</b> One individual from Devon presented with laterocollis [<a class="bibr" href="#sca11.REF.giunti.2012" rid="sca11.REF.giunti.2012">Giunti et al 2012</a>]. Dystonia has not been described in other individuals.</p><p><b>Prognosis.</b> SCA11 is slowly progressive with severity ranging from very mild balance problems at disease onset, to severe speech and swallowing problems and ataxia requiring the use of a wheelchair. In affected individuals from the British and Pakistani families, eight of 17 persons required a wheelchair 20 to 30 years after onset. The same was reported in the French and German families, where progression of disease is slow; individuals remained active many years and required a wheelchair decades after onset [<a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>]. Life span in individuals with SCA11 is normal; many affected individuals live beyond age 75 years. In nine individuals from the British and Pakistani families, death occurred between ages 55 and 88 years.</p><p><b>Neuroimaging.</b> Brain MRI examination shows mild-to-severe atrophy in both cerebellar hemispheres and the vermis. The brain stem and cerebrum were normal in most individuals [<a class="bibr" href="#sca11.REF.giunti.2012" rid="sca11.REF.giunti.2012">Giunti et al 2012</a>]. Occasionally, atrophy has also been described in the medulla but this was not associated with disease severity [<a class="bibr" href="#sca11.REF.giunti.2012" rid="sca11.REF.giunti.2012">Giunti et al 2012</a>, <a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al 2020</a>]. In a Danish proband, an 18Ffluorodeoxyglucose positron emission tomography scan showed reduced metabolic activity in the cerebellum and pons, and repeat brain MRI four years later showed worsening cerebellar atrophy with olivopontine atrophy [<a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>].</p><p><b>Neuropathology.</b> Neuropathologic examination of the brain of one affected individual showed marked cerebellar and brain stem loss with Purkinje cell degeneration and abnormal tau deposition in the brain stem and cortex [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>].</p></div><div id="sca11.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations have been identified.</p></div><div id="sca11.Penetrance"><h3>Penetrance</h3><p>The <i>TTBK2</i> pathogenic variants in the six families described to date appear to be fully penetrant, although a number of at-risk relatives are younger than the typical age of onset. To date, no non-penetrant pathogenic variants have been identified in older individuals.</p></div><div id="sca11.Prevalence"><h3>Prevalence</h3><p>Prevalence is unknown but SCA11 is a rare cause of pure spinocerebellar ataxia. It accounts for less than 1% of autosomal dominant ataxia in Europe [<a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>]. Pathogenic variants in <i>TTBK2</i> were identified in six of 238 families with spinocerebellar ataxia [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>; <a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>; Author, personal observation]. A study in Germany of 49 individuals with a family history of ataxia did not identify pathogenic variants in <i>TTBK2</i> [<a class="bibr" href="#sca11.REF.edener.2009.1856" rid="sca11.REF.edener.2009.1856">Edener et al 2009</a>]. A study in China of 68 unrelated probands with autosomal dominant ataxia also did not identify pathogenic variants in <i>TTBK2</i> [<a class="bibr" href="#sca11.REF.xu.2010.107" rid="sca11.REF.xu.2010.107">Xu et al 2010</a>].</p><p>The six families described with SCA11 are from Devon (UK), Pakistan, France, Germany, Denmark, and China.</p></div></div><div id="sca11.Genetically_Related_Allelic_Disord"><h2 id="_sca11_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>TTBK2</i>.</p></div><div id="sca11.Differential_Diagnosis"><h2 id="_sca11_Differential_Diagnosis_">Differential Diagnosis</h2><p>According to AE Harding's classification, spinocerebellar ataxia type 11 (SCA11) is included in the pure autosomal dominant cerebellar ataxias (ADCA III) [<a class="bibr" href="#sca11.REF.worth.1999.420" rid="sca11.REF.worth.1999.420">Worth et al 1999</a>], the most common group of inherited ataxias. SCA11 accounts for approximately 2% of ADCA III.</p><p>Significant overlap is observed between SCA11 and SCA5, <a href="/books/n/gene/sca6/?report=reader">SCA6</a>, SCA15, and <a href="/books/n/gene/sca20/?report=reader">SCA20</a>, all of which may be distinguished by molecular genetic testing (see <a href="/books/NBK1757/table/sca11.T.hereditary_ataxia_disorders_of_i/?report=objectonly" target="object" rid-ob="figobsca11Thereditaryataxiadisordersofi">Table 3</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Thereditaryataxiadisordersofi"><a href="/books/NBK1757/table/sca11.T.hereditary_ataxia_disorders_of_i/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobsca11Thereditaryataxiadisordersofi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.hereditary_ataxia_disorders_of_i"><a href="/books/NBK1757/table/sca11.T.hereditary_ataxia_disorders_of_i/?report=objectonly" target="object" rid-ob="figobsca11Thereditaryataxiadisordersofi">Table 3. </a></h4><p class="float-caption no_bottom_margin">Hereditary Ataxia Disorders of Interest in the Differential Diagnosis of Spinocerebellar Ataxia Type 11 </p></div></div><p>See the <a href="/books/n/gene/ataxias/?report=reader">Hereditary Ataxia Overview</a> for information on other types of inherited (genetic) ataxia.</p></div><div id="sca11.Management"><h2 id="_sca11_Management_">Management</h2><p>Management is supportive; a multidisciplinary approach is recommended.</p><div id="sca11.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with spinocerebellar ataxia type 11 (SCA11), the evaluations summarized in <a href="/books/NBK1757/table/sca11.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobsca11Trecommendedevaluationsfollowin">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Trecommendedevaluationsfollowin"><a href="/books/NBK1757/table/sca11.T.recommended_evaluations_followin/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobsca11Trecommendedevaluationsfollowin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.recommended_evaluations_followin"><a href="/books/NBK1757/table/sca11.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobsca11Trecommendedevaluationsfollowin">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Spinocerebellar Ataxia Type 11 </p></div></div></div><div id="sca11.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management is supportive; no disease-modifying treatments are known to date.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Ttreatmentofmanifestationsini"><a href="/books/NBK1757/table/sca11.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobsca11Ttreatmentofmanifestationsini"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.treatment_of_manifestations_in_i"><a href="/books/NBK1757/table/sca11.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" rid-ob="figobsca11Ttreatmentofmanifestationsini">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with SCA11 </p></div></div></div><div id="sca11.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Trecommendedsurveillanceforind"><a href="/books/NBK1757/table/sca11.T.recommended_surveillance_for_ind/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobsca11Trecommendedsurveillanceforind"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.recommended_surveillance_for_ind"><a href="/books/NBK1757/table/sca11.T.recommended_surveillance_for_ind/?report=objectonly" target="object" rid-ob="figobsca11Trecommendedsurveillanceforind">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with SCA11 </p></div></div></div><div id="sca11.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#sca11.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="sca11.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="sca11.Genetic_Counseling"><h2 id="_sca11_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="sca11.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Spinocerebellar ataxia type 11 (SCA11) is inherited in an autosomal dominant manner.</p></div><div id="sca11.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>Twenty-seven of 28 of individuals diagnosed with SCA11 have an affected parent.</div></li><li class="half_rhythm"><div>A proband with SCA11 may have the disorder as the result of a <i>de novo</i>
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<i>TTBK2</i> pathogenic variant. The proportion of cases caused by <i>de novo</i> variants is unknown but likely small. To date, <i>de novo</i> SCA11 has been seen in one individual, from the family of Danish origin [<a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband with an apparent <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div>If the pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, possible explanations include a <i>de novo</i> pathogenic variant in the proband or germline mosaicism in a parent (though theoretically possible, no instances of germline mosaicism have been reported).</div></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with SCA11 may appear to be negative because of failure to recognize the disorder in family members with a milder phenotypic presentation, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. Therefore, an apparently negative family history cannot be confirmed unless appropriate molecular genetic testing has been performed on the parents of the proband.</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of a proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs is 50%. Age of onset may vary within a family.</div></li><li class="half_rhythm"><div>If the proband has a known SCA11-related pathogenic variant that cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism [<a class="bibr" href="#sca11.REF.rahbari.2016.126" rid="sca11.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>TTBK2</i> pathogenic variant but are clinically unaffected, sibs are still presumed to be at increased risk for SCA11 because of the possibility of age-related penetrance in a heterozygous parent or the theoretic possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with SCA11 has a 50% chance of inheriting the <i>TTBK2</i> pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent has the pathogenic variant, his or her family members may be at risk.</p></div><div id="sca11.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Predictive testing (i.e., testing of asymptomatic at-risk individuals)</b>
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</p><ul><li class="half_rhythm"><div>Predictive testing for at-risk relatives is possible once the <i>TTBK2</i> pathogenic variant has been identified in an affected family member. Such testing is not useful in accurately predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals.</div></li><li class="half_rhythm"><div>Potential consequences of such testing (including but not limited to socioeconomic changes and the need for long-term follow up and evaluation arrangements for individuals with a positive test result) as well as the capabilities and limitations of predictive testing should be discussed in the context of formal genetic counseling prior to testing.</div></li></ul><p>
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<b>Predictive testing in minors (i.e., testing of asymptomatic at-risk individuals age <18 years)</b>
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</p><ul><li class="half_rhythm"><div>For asymptomatic minors at risk for adult-onset conditions for which early treatment would have no beneficial effect on disease morbidity and mortality, predictive genetic testing is considered inappropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.</div></li><li class="half_rhythm"><div>For more information, see the National Society of Genetic Counselors <a href="https://www.nsgc.org/Policy-Research-and-Publications/Position-Statements/Position-Statements/Post/genetic-testing-of-minors-for-adult-onset-conditions" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">position statement</a> on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics <a href="https://pediatrics.aappublications.org/content/131/3/620.full.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">policy statement</a>: ethical and policy issues in genetic testing and screening of children.</div></li></ul><p>In a family with an established diagnosis of SCA11, it is appropriate to consider testing of symptomatic individuals regardless of age.</p><p><b>Considerations in families with an apparent <i>de novo</i> pathogenic variant.</b> When neither parent of a proband with an autosomal dominant condition has the pathogenic variant identified in the proband or clinical evidence of the disorder, the pathogenic variant is likely <i>de novo</i>. However, non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) and undisclosed adoption could also be explored.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul></div><div id="sca11.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>TTBK2</i> pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="sca11.Resources"><h2 id="_sca11_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>NCBI Genes and Disease</b>
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</div><div>
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<a href="https://www.ncbi.nlm.nih.gov/books/NBK22234/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Spinocerebellar ataxia</a>
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</div></li><li class="half_rhythm"><div>
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<b>Ataxia UK</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 0800 995 6037; +44 (0) 20 7582 1444 (from abroad)</div><div><b>Email:</b> help@ataxia.org.uk</div><div>
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<a href="https://www.ataxia.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ataxia.org.uk</a>
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</div></li><li class="half_rhythm"><div>
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<b>euro-ATAXIA (European Federation of Hereditary Ataxias)</b>
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</div><div>United Kingdom</div><div><b>Email:</b> ageorgousis@ataxia.org.uk</div><div>
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<a href="https://www.euroataxia.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">euroataxia.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Ataxia Foundation</b>
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</div><div><b>Phone:</b> 763-553-0020</div><div><b>Email:</b> naf@ataxia.org</div><div>
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<a href="https://www.ataxia.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ataxia.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Spanish Ataxia Federation (FEDAES)</b>
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</div><div>Spain</div><div><b>Phone:</b> 601 037 982</div><div><b>Email:</b> info@fedaes.org</div><div>
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<a href="https://fedaes.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">fedaes.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>CoRDS Registry</b>
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</div><div>Sanford Research</div><div><b>Phone:</b> 605-312-6300</div><div>
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<a href="https://research.sanfordhealth.org/rare-disease-registry" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CoRDS Registry</a>
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</div></li></ul>
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</div><div id="sca11.Molecular_Genetics"><h2 id="_sca11_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11molgenTA"><a href="/books/NBK1757/table/sca11.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobsca11molgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.molgen.TA"><a href="/books/NBK1757/table/sca11.molgen.TA/?report=objectonly" target="object" rid-ob="figobsca11molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Spinocerebellar Ataxia Type 11: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11molgenTB"><a href="/books/NBK1757/table/sca11.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobsca11molgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.molgen.TB"><a href="/books/NBK1757/table/sca11.molgen.TB/?report=objectonly" target="object" rid-ob="figobsca11molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Spinocerebellar Ataxia Type 11 (View All in OMIM) </p></div></div><div id="sca11.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>TTBK2</i> encodes tau-tubulin kinase 2 (TTBK2), which modifies targets such as tau and tubulin, to initiate ciliogenesis [<a class="bibr" href="#sca11.REF.goetz.2012.847" rid="sca11.REF.goetz.2012.847">Goetz et al 2012</a>]. TTBK2 phosphorylates the tau protein to exacerbate tau toxicity as well as TDP43, driving neurodegeneration [<a class="bibr" href="#sca11.REF.taylor.2018.7" rid="sca11.REF.taylor.2018.7">Taylor et al 2018</a>]. Abnormal tau deposition has been described in SCA11, further implicating the direct link between <i>TTBK2</i> and tauopathic disease [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>].</p><p>Non-ciliary functions of TTBK2 within the brain include phosphorylation of synaptic vesicle protein 2A (SV2A), which is important for synaptic vesicle trafficking and regulation of neurotransmitter release [<a class="bibr" href="#sca11.REF.zhang.2015.2492" rid="sca11.REF.zhang.2015.2492">Zhang et al 2015</a>]. TTBK2 has also been implicated in regulation of sodium-coupled transporters [<a class="bibr" href="#sca11.REF.alesutan.2012.458" rid="sca11.REF.alesutan.2012.458">Alesutan et al 2012</a>].</p><p>Loss of TTBK2 function affects normal phosphorylation of tau, which leads to tau deposition and impaired ciliogenesis. There is evidence that TTBK2 may interact with the inositol/IP3 pathway and stabilize cells (in particular, Purkinje cells) against calcium-induced cell death [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>] (see <a href="https://www.biorxiv.org/content/10.1101/689448v1.full" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">bioRxiv</a>).</p><p><b>Mechanism of disease causation.</b> Reported <i>TTBK2</i> pathogenic variants are predicted to result in premature stop codons, and individuals with SCA11-associated <i>TTBK2</i> variants were reported to have mRNA levels reduced by 50% when compared to unaffected individuals [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. Further, treating lymphoblasts from affected individuals with cycloheximide, a known inhibitor of nonsense-mediated decay (NMD), resulted in increased total <i>TTBK2</i> mRNA and a selective increase in the abundance of the mutated mRNA, suggesting that a proportion of the abnormal mRNA escapes NMD [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>]. This means that a truncated protein could be produced, causing a dominant-negative effect on the normal allele. A recent study showed that the abnormal truncated protein can disrupt function of the residual normal protein in cilium assembly, stability, and signaling, supporting a dominant-negative effect [<a class="bibr" href="#sca11.REF.bowie.2018.e1007844" rid="sca11.REF.bowie.2018.e1007844">Bowie et al 2018</a>].</p><p>Further supporting the dominant-negative effect is the presence of other reported heterozygous frameshift variants clustered in exon 11, leading to truncation of the TTBK2 protein C-terminal to the kinase domain at amino acid 450 [<a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>] and truncation at amino acid 402 [<a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>] – suggesting a dominant-negative effect exerted by the truncated protein. One missense variant has recently been described in the Chinese population but the mechanism for this is unclear.</p><p>No gene-dosage alterations have been detected in <i>TTBK2</i>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsca11Tnotablettbk2pathogenicvariant"><a href="/books/NBK1757/table/sca11.T.notable_ttbk2_pathogenic_variant/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobsca11Tnotablettbk2pathogenicvariant"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="sca11.T.notable_ttbk2_pathogenic_variant"><a href="/books/NBK1757/table/sca11.T.notable_ttbk2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobsca11Tnotablettbk2pathogenicvariant">Table 7. </a></h4><p class="float-caption no_bottom_margin">Notable <i>TTBK2</i> Pathogenic Variants </p></div></div></div></div><div id="sca11.References"><h2 id="_sca11_References_">References</h2><div id="sca11.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.alesutan.2012.458">Alesutan I, Sopjani M, Dërmaku-Sopjani M, Munoz C, Voelkl J, Lang F. Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2. <span><span class="ref-journal">Cell Physiol Biochem. </span>2012;2012;<span class="ref-vol">30</span>:458–65.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22814243" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22814243</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.bauer.2010.1229">Bauer P, Stevanin G, Beetz C, Synofzik M, Schmitz-Hübsch T, Wüllner U, Berthier E, Ollagnon-Roman E, Riess O, Forlani S, Mundwiller E, Durr A, Schöls L, Brice A. Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds. <span><span class="ref-journal">J Neurol Neurosurg Psychiatry. </span>2010;<span class="ref-vol">81</span>:1229–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20667868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20667868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.bowie.2018.e1007844">Bowie E, Norris R, Anderson KV, Goetz SC. Spinocerebellar ataxia type 11-associated alleles of Ttbk2 dominantly interfere with ciliogenesis and cilium stability. <span><span class="ref-journal">PLoS Genet. </span>2018;<span class="ref-vol">14</span>:e1007844. </span> [<a href="/pmc/articles/PMC6307817/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6307817</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30532139" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30532139</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.deng.2020.155">Deng Y, Fu J, Zhong Y, Zhang M, Qi X. First finding of familial spinal cerebellar ataxia 11 in China: clinical, imaging and genetic features. <span><span class="ref-journal">Neurol Sci. </span>2020;<span class="ref-vol">41</span>:155–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31485862" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31485862</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.edener.2009.1856">Edener U, Kurth I, Meiner A, Hoffmann F, Hübner CA, Bernard V, Gillessen-Kaesbach G, Zühlke C. Missense exchanges in the TTBK2 gene mutated in SCA11. <span><span class="ref-journal">J Neurol. </span>2009;<span class="ref-vol">256</span>:1856–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19533200" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19533200</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.giunti.2012">Giunti P, Houlden H, Gardner-Thorpe C, Worth PF, Johnson J, Hilton DA, Revesz T, Davis MB, Wood NW. Spinocerebellar ataxia type 11. In: Aminoff MJ, Boller F, Swaab D, eds. <em>Handbook of Clinical Neurology</em>. Vol 103. Elsevier; 2012: 521-34. [<a href="https://pubmed.ncbi.nlm.nih.gov/21827911" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21827911</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.goetz.2012.847">Goetz SC, Liem KF Jr, Anderson KV. The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis. <span><span class="ref-journal">Cell. </span>2012;<span class="ref-vol">151</span>:847–58.</span> [<a href="/pmc/articles/PMC3496184/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3496184</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23141541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23141541</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.houlden.2007.1434">Houlden H, Johnson J, Gardner-Thorpe C, Lashley T, Hernandez D, Worth P, Singleton AB, Hilton DA, Holton J, Revesz T, Davis MB, Giunti P, Wood NW. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. <span><span class="ref-journal">Nat Genet. </span>2007;<span class="ref-vol">39</span>:1434–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18037885" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18037885</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.lindquist.2017.268">Lindquist SG, Møller LB, Dali CI, Marner L, Kamsteeg E-J, Nielsen JE, Hjermind LE. A novel TTBK2 de novo mutation in a Danish family with early-onset spinocerebellar ataxia. <span><span class="ref-journal">Cerebellum. </span>2017;<span class="ref-vol">16</span>:268–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27165044" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27165044</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.rahbari.2016.126">Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB, Turki SA, Dominiczak A, Morris A, Porteous D, Smith B, Stratton MR, Hurles ME, et al. Timing, rates and spectra of human germline mutation. <span><span class="ref-journal">Nat Genet. </span>2016;<span class="ref-vol">48</span>:126–33.</span> [<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.taylor.2018.7">Taylor LM, McMillan PJ, Liachko NF, Strovas TJ, Ghetti B, Bird TD, Keene CD, Kraemer BC. Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration. <span><span class="ref-journal">Mol Neurodegener. </span>2018;<span class="ref-vol">13</span>:7.</span> [<a href="/pmc/articles/PMC5802059/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5802059</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29409526" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29409526</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.worth.1999.420">Worth PF, Giunti P, Gardner-Thorpe C, Dixon PH, Davis MB, Wood NW. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. <span><span class="ref-journal">Am J Hum Genet. </span>1999;<span class="ref-vol">65</span>:420–6.</span> [<a href="/pmc/articles/PMC1377940/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1377940</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10417284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10417284</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.xu.2010.107">Xu Q, Li X, Wang J, Yi J, Lei L, Shen L, Jiang H, Xia K, Pan Q, Tang B. Spinocerebellar ataxia type 11 in the Chinese Han population. <span><span class="ref-journal">Neurol Sci. </span>2010;<span class="ref-vol">31</span>:107–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19768375" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19768375</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sca11.REF.zhang.2015.2492">Zhang N, Gordon SL, Fritsch MJ, Esoof N, Campbell DG, Gourlay R, Velupillai S, Macartney T, Peggie M, van Aalten DM, Cousin MA, Alessi DR. Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1. <span><span class="ref-journal">J Neurosci. </span>2015;<span class="ref-vol">35</span>:2492–507.</span> [<a href="/pmc/articles/PMC4323530/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4323530</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25673844" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25673844</span></a>]</div></p></li></ul></div></div><div id="sca11.Chapter_Notes"><h2 id="_sca11_Chapter_Notes_">Chapter Notes</h2><div id="sca11.Acknowledgments"><h3>Acknowledgments</h3><p>We are grateful to the Medical Research Council (MRC) for their support: HH holds an MRC clinician scientist fellowship. This work was also supported by the NIHR UCL/UCLH biomedical research centre (BRC). ZC was supported by a fellowship from the Leonard Wolfson Foundation. We thank the families involved and the organization Ataxia UK for their continued support and assistance with our work.</p></div><div id="sca11.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>31 October 2019 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 March 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>22 July 2008 (me) Review posted live</div></li><li class="half_rhythm"><div>9 June 2008 (hh) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1757_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Zhongbo Chen</span>, MA, BM BCh, MRCP<div class="affiliation small">Department of Neurodegenerative Disease
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UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery
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London, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.lcu@nehc.obgnohz" class="oemail">ku.ca.lcu@nehc.obgnohz</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Arina Puzriakova</span>, BSc, MSc<div class="affiliation small">Department of Neuromuscular Disease
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UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery
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London, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.lcu@81.avokairzup.anira" class="oemail">ku.ca.lcu@81.avokairzup.anira</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Henry Houlden</span>, MD, PhD<div class="affiliation small">Department of Neuromuscular Disease
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UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery
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London, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.lcu@nedluoh.h" class="oemail">ku.ca.lcu@nedluoh.h</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">July 22, 2008</span>; Last Update: <span itemprop="dateModified">October 31, 2019</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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a registered trademark of the University of Washington, Seattle. All rights
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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Washington) are included with each copy; (ii) a link to the original material is provided
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distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Chen Z, Puzriakova A, Houlden H. Spinocerebellar Ataxia Type 11. 2008 Jul 22 [Updated 2019 Oct 31]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/sca10/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/sca12/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobsca11Tmoleculargenetictestingusedi"><div id="sca11.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Spinocerebellar Ataxia Type 11</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TTBK2</i>
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</td><td headers="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/6 families <sup>4</sup></td></tr><tr><td headers="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_sca11.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>6</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sca11.TF.1.1"><p class="no_margin">See <a href="/books/NBK1757/?report=reader#sca11.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="sca11.TF.1.2"><p class="no_margin">See <a href="#sca11.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="sca11.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="sca11.TF.1.4"><p class="no_margin"><a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al [2007]</a>, <a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al [2010]</a>, <a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al [2017]</a>, <a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al [2020]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="sca11.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="sca11.TF.1.6"><p class="no_margin">No data on detection rate of gene-targeted deletion/duplication analysis are available.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsca11Tclinicalfeaturesofspinocerebe"><div id="sca11.T.clinical_features_of_spinocerebe" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Clinical Features of Spinocerebellar Ataxia Type 11</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.clinical_features_of_spinocerebe/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.clinical_features_of_spinocerebe_lrgtbl__"><table><thead><tr><th id="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Number of Persons w/Feature</th><th id="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cerebellar ataxia</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">28/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Variable truncal &/or gait ataxia</td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Limb ataxia</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysarthria</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Jerky pursuit</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Nystagmus</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmoplegia</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Diplopia</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hyperreflexia</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Most prominent in the British family</div></li><li class="half_rhythm"><div>Lower > upper limbs</div></li></ul>
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</td></tr><tr><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Extrapyramidal</b>
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<br />
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<b>features</b>
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</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/28</td><td headers="hd_h_sca11.T.clinical_features_of_spinocerebe_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Laterocollis</div></li><li class="half_rhythm"><div>"No-no" head tremor</div></li></ul>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobsca11Thereditaryataxiadisordersofi"><div id="sca11.T.hereditary_ataxia_disorders_of_i" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Hereditary Ataxia Disorders of Interest in the Differential Diagnosis of Spinocerebellar Ataxia Type 11</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.hereditary_ataxia_disorders_of_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.hereditary_ataxia_disorders_of_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Key Clinical Features</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CACNA1A</i>
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</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/sca6/?report=reader">SCA6</a>
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</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pure cerebellar ataxia w/slow progression. Some described w/downbeat nystagmus, whereas 50% of British individuals w/SCA11 had an upbeat nystagmus.</td></tr><tr><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ITPR1</i>
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</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/sca15/?report=reader">SCA15</a> (OMIM <a href="https://omim.org/entry/606658" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">606658</a>)</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Slowly progressive pure cerebellar ataxia w/mild tremor & mild hyperreflexia</td></tr><tr><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SPTBN2</i>
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</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SCA5 (OMIM <a href="https://omim.org/entry/600224" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">600224</a>)</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Slowly progressive pure cerebellar ataxia</td></tr><tr><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>1</sup></td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/sca20/?report=reader">SCA20</a>
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</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sca11.T.hereditary_ataxia_disorders_of_i_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Slowly progressive cerebellar ataxia w/abnormal phonation & dysarthria, & palatal tremor in 2/3s of individuals. Minor pyramidal signs may also be seen.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; MOI = mode of inheritance; SCA = spinocerebellar ataxia</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sca11.TF.3.1"><p class="no_margin">The locus for SCA20 lies within the pericentromeric region of chromosome 11; the gene is unknown. A 260-kb duplication of 11q12.2-11q12.3 has been proposed as the probable cause of SCA20 in the index family.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsca11Trecommendedevaluationsfollowin"><div id="sca11.T.recommended_evaluations_followin" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Spinocerebellar Ataxia Type 11</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.recommended_evaluations_followin/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.recommended_evaluations_followin_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Use SARA to establish baseline.</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Head MRI</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Initial imaging to establish extent of cerebellar atrophy at disease presentation</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Feeding eval</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for bulbar involvement that may require intervention (e.g., adjustment to dietary consistency to improve safe swallow)</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Speech & language therapy eval</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If dysarthria is atypical or severe enough to cause communication problems</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">PT & OT eval</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate mobility, activities of daily living, & need for adaptive devices</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Peripheral nervous system</b>
|
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</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nerve conduction studies</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nerve conduction studies recommended to exclude a coexisting neuropathy that may require further monitoring</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Ophthalmologic</b>
|
|
</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate eye movement & for diplopia</td></tr><tr><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Other</b>
|
|
</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_sca11.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy; SARA = Scale for the Assessment and Rating of Ataxia</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsca11Ttreatmentofmanifestationsini"><div id="sca11.T.treatment_of_manifestations_in_i" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with SCA11</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.treatment_of_manifestations_in_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.treatment_of_manifestations_in_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation<br />Concern</th><th id="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ataxia</b>
|
|
</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>PT eval/treatment</div></li><li class="half_rhythm"><div>OT eval/treatment</div></li></ul>
|
|
</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider adaptive devices (cane &/or wheelchair) & home adaptations to maintain/improve independent mobility.</td></tr><tr><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Weight control</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To facilitate ambulation</td></tr><tr><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Dysarthria &</b>
|
|
<br />
|
|
<b>dysphagia</b>
|
|
</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech & language therapy eval/treatment</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To teach strategies to improve articulation & avoid aspiration</td></tr><tr><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Modify food consistency to reduce aspiration risk</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Video esophagram may help define best consistency.</td></tr><tr><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Peripheral</b>
|
|
<br />
|
|
<b>neuropathy</b>
|
|
</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ankle-foot orthotics</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ensure good foot care & foot health w/regular review by podiatrist.</td></tr><tr><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Diplopia</b>
|
|
</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic consultation</td><td headers="hd_h_sca11.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prism glasses can be helpful.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsca11Trecommendedsurveillanceforind"><div id="sca11.T.recommended_surveillance_for_ind" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with SCA11</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.recommended_surveillance_for_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.recommended_surveillance_for_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Ataxia</b>
|
|
</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">PT & OT</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ideally, in the context of a multidisciplinary setting w/more intensive follow up if needed</td></tr><tr><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysarthria &</b>
|
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<br />
|
|
<b>dysphagia</b>
|
|
</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval w/speech-language pathologist</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Follow up dependent on severity & requirements</td></tr><tr><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmoplegia</b>
|
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<br />
|
|
<b>& diplopia</b>
|
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</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology</td><td headers="hd_h_sca11.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Follow up dependent on severity & requirements</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsca11molgenTA"><div id="sca11.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Spinocerebellar Ataxia Type 11: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_sca11.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_sca11.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_sca11.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_sca11.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_sca11.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_sca11.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_sca11.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="/gene/146057" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>TTBK2</i>
|
|
</a>
|
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</td><td headers="hd_b_sca11.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=146057" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">15q15<wbr style="display:inline-block"></wbr>​.2</a>
|
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</td><td headers="hd_b_sca11.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.uniprot.org/uniprot/Q6IQ55" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Tau-tubulin kinase 2</a>
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</td><td headers="hd_b_sca11.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/TTBK2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TTBK2 database</a>
|
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</td><td headers="hd_b_sca11.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=TTBK2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TTBK2</a>
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</td><td headers="hd_b_sca11.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=TTBK2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TTBK2</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="sca11.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsca11molgenTB"><div id="sca11.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Spinocerebellar Ataxia Type 11 (<a href="/omim/604432,611695" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604432" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604432</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPINOCEREBELLAR ATAXIA 11; SCA11</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/611695" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611695</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TAU TUBULIN KINASE 2; TTBK2</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobsca11Tnotablettbk2pathogenicvariant"><div id="sca11.T.notable_ttbk2_pathogenic_variant" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>TTBK2</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1757/table/sca11.T.notable_ttbk2_pathogenic_variant/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sca11.T.notable_ttbk2_pathogenic_variant_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequencies</th><th id="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change (Alias <sup>1</sup>)</th><th id="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_173500.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_173500<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_775771.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_775771<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1205_1207delinsA</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Thr402fs</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_4" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Pathogenic variants clustered in exon 11 [<a class="bibr" href="#sca11.REF.houlden.2007.1434" rid="sca11.REF.houlden.2007.1434">Houlden et al 2007</a>, <a class="bibr" href="#sca11.REF.bauer.2010.1229" rid="sca11.REF.bauer.2010.1229">Bauer et al 2010</a>, <a class="bibr" href="#sca11.REF.lindquist.2017.268" rid="sca11.REF.lindquist.2017.268">Lindquist et al 2017</a>]</td></tr><tr><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1287_1288delAG<br />(1284_1285delAG)</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu429AspfsTer21</td></tr><tr><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1306_1307delGA</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asp435TyrfsTer14</td></tr><tr><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1329dupA<br />(1329insA)</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg444ThrfsTer7</td></tr><tr><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.3290T>C</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val1097Ala</td><td headers="hd_h_sca11.T.notable_ttbk2_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Missense variant identified in a 3-generation Chinese family w/5 individuals w/adult-onset ataxia [<a class="bibr" href="#sca11.REF.deng.2020.155" rid="sca11.REF.deng.2020.155">Deng et al 2020</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sca11.TF.7.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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