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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Troyer Syndrome - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Troyer Syndrome">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2019/06/06">
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<meta name="citation_author" content="Emma Baple">
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<meta name="citation_author" content="Andrew Crosby">
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<meta name="citation_pmid" content="20301556">
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<meta name="citation_keywords" content="SPG20">
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<meta name="citation_keywords" content="Spartin">
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<meta name="citation_keywords" content="SPART">
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<meta name="citation_keywords" content="Troyer Syndrome">
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<meta name="DC.Title" content="Troyer Syndrome">
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<meta name="DC.Contributor" content="Emma Baple">
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<meta name="DC.Contributor" content="Andrew Crosby">
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<meta name="description" content="Troyer syndrome is characterized by progressive spastic paraparesis, dysarthria, pseudobulbar palsy, distal amyotrophy, short stature, and subtle skeletal abnormalities. Most affected children exhibit delays in walking and speech and difficulty in managing oral secretions, followed by increased lower-limb spasticity and slow deterioration in both gait and speech. Mild cerebellar signs are common. The most severely affected individuals have choreoathetosis. Emotional lability / difficulty in controlling emotions and affective disorders, such as inappropriate euphoria and/or crying, are frequently described. Life expectancy is normal.">
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<meta name="og:description" content="Troyer syndrome is characterized by progressive spastic paraparesis, dysarthria, pseudobulbar palsy, distal amyotrophy, short stature, and subtle skeletal abnormalities. Most affected children exhibit delays in walking and speech and difficulty in managing oral secretions, followed by increased lower-limb spasticity and slow deterioration in both gait and speech. Mild cerebellar signs are common. The most severely affected individuals have choreoathetosis. Emotional lability / difficulty in controlling emotions and affective disorders, such as inappropriate euphoria and/or crying, are frequently described. Life expectancy is 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="_NBK1382_"><span class="title" itemprop="name">Troyer Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: SPG20</div><p class="contribs">Baple E, Crosby A.</p><p class="fm-aai"><a href="#_NBK1382_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 14 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="spg20.Summary" itemprop="description"><h2 id="_spg20_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Troyer syndrome is characterized by progressive spastic paraparesis, dysarthria, pseudobulbar palsy, distal amyotrophy, short stature, and subtle skeletal abnormalities. Most affected children exhibit delays in walking and speech and difficulty in managing oral secretions, followed by increased lower-limb spasticity and slow deterioration in both gait and speech. Mild cerebellar signs are common. The most severely affected individuals have choreoathetosis. Emotional lability / difficulty in controlling emotions and affective disorders, such as inappropriate euphoria and/or crying, are frequently described. Life expectancy is normal.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of Troyer syndrome is established in an individual with characteristic clinical findings. Identification of biallelic pathogenic variants in <i>SPART</i> confirms the diagnosis if clinical features are inconclusive.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Antispasticity drugs; daily physical therapy; occupational therapy, assistive walking devices, and ankle-foot orthotics as needed; antidepressant or mood stabilizer medication for individuals with emotional lability.</p><p><i>Surveillance:</i> Neurologic and developmental/cognitive assessments; monitoring for dysphagia to reduce the risk of aspiration.</p><p><i>Agents/circumstances to avoid:</i> Dantrolene should be avoided in persons who are ambulatory as it may induce irreversible weakness, which can adversely interfere with overall mobility.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Troyer syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both pathogenic variants have been identified in an affected family member.</p></div></div><div id="spg20.Diagnosis"><h2 id="_spg20_Diagnosis_">Diagnosis</h2><div id="spg20.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Troyer syndrome <b>should be suspected</b> in individuals with the following findings:</p><p>
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<b>Clinical features</b>
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</p><ul><li class="half_rhythm"><div>Childhood-onset spastic paraplegia</div></li><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Persistent drooling</div></li><li class="half_rhythm"><div>Symmetric amyotrophy of the small muscles of hands and feet</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Emotional lability</div></li></ul><p>
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<b>Additional clinical features</b>
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</p><ul><li class="half_rhythm"><div>At birth: low/low-normal birth weight, relative macrocephaly, triangular face shape, poor feeding</div></li><li class="half_rhythm"><div>Early infancy / childhood: delayed walking, delayed speech, swallowing difficulties</div></li><li class="half_rhythm"><div>Pyramidal signs: hyperreflexia, extensor plantar responses</div></li><li class="half_rhythm"><div>Extrapyramidal signs: mild choreoathetoid movements</div></li><li class="half_rhythm"><div>Cerebellar signs: dysdiadochokinesia, mild intention tremor</div></li><li class="half_rhythm"><div>Skeletal abnormalities: <i>pes cavus</i>, mild <i>talipes equinovarus</i>, kyphoscoliosis</div></li><li class="half_rhythm"><div>Mild to moderate intellectual disability</div></li></ul><p><b>Imaging features on brain MRI.</b> White matter abnormalities, particularly in the temporoparietal periventricular area (3/3 affected individuals)</p></div><div id="spg20.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of Troyer syndrome <b>is established</b> in a proband with childhood-onset spastic paraplegia, distal amyotrophy, short stature, and/or biallelic pathogenic variants in <i>SPART</i> identified by molecular genetic testing (see <a href="/books/NBK1382/table/spg20.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobspg20Tmoleculargenetictestingusedi">Table 1</a>).</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Troyer syndrome is broad, individuals with the distinctive findings described in <a href="#spg20.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#spg20.Option_1">Option 1</a>), whereas those in whom the diagnosis of Troyer syndrome has not been considered are more likely to be diagnosed using genomic testing (see <a href="#spg20.Option_2">Option 2</a>).</p><div id="spg20.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of Troyer syndrome, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>SPART</i> detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.</div><div class="half_rhythm">Note: Targeted analysis for pathogenic variant <a href="/books/NBK1382/table/spg20.T.spart_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobspg20Tspartpathogenicvariantsdiscus">c.1110delA</a> can be performed first in individuals of Amish ancestry [<a class="bibr" href="#spg20.REF.patel.2002.347" rid="spg20.REF.patel.2002.347">Patel et al 2002</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A hereditary spastic paraplegia</b>
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<b>multigene panel</b> that includes <i>SPART</i> and other genes of interest (see <a href="#spg20.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 Troyer syndrome, some panels for hereditary spastic paraplegia 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></ul></div><div id="spg20.Option_2"><h4>Option 2</h4><p>When the diagnosis of Troyer syndrome is not considered because an individual has atypical phenotypic features, <b>comprehensive genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is the best option. <b>Exome sequencing</b> is the most commonly used genomic testing method; <b>genome sequencing</b> is also possible.</p><p>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>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figspg20Tmoleculargenetictestingusedi"><a href="/books/NBK1382/table/spg20.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobspg20Tmoleculargenetictestingusedi"><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="spg20.T.molecular_genetic_testing_used_i"><a href="/books/NBK1382/table/spg20.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobspg20Tmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Troyer Syndrome </p></div></div></div></div></div><div id="spg20.Clinical_Characteristics"><h2 id="_spg20_Clinical_Characteristics_">Clinical Characteristics</h2><div id="spg20.Clinical_Description"><h3>Clinical Description</h3><p>Troyer syndrome is characterized by both developmental and neurodegenerative processes. Symptoms are usually apparent in early childhood and progress slowly. The cardinal features of Troyer syndrome include developmental delay, spastic paraparesis, dysarthria, distal amyotrophy, and short stature. To date, 36 individuals with Troyer syndrome have been reported, including 21 individuals from an Old Order Amish population in Ohio, USA [<a class="bibr" href="#spg20.REF.patel.2002.347" rid="spg20.REF.patel.2002.347">Patel et al 2002</a>, <a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>, <a class="bibr" href="#spg20.REF.manzini.2010.516" rid="spg20.REF.manzini.2010.516">Manzini et al 2010</a>, <a class="bibr" href="#spg20.REF.tawamie.2015.315" rid="spg20.REF.tawamie.2015.315">Tawamie et al 2015</a>, <a class="bibr" href="#spg20.REF.butler.2016.1780" rid="spg20.REF.butler.2016.1780">Butler et al 2016</a>, <a class="bibr" href="#spg20.REF.dardour.2017" rid="spg20.REF.dardour.2017">Dardour et al 2017</a>, <a class="bibr" href="#spg20.REF.spiegel.2017.55" rid="spg20.REF.spiegel.2017.55">Spiegel et al 2017</a>].</p><p><b>Onset.</b> Clinical features that may be recognized from birth in the Amish, where the condition occurs at an increased frequency, include low birth weight, relative macrocephaly, triangular face shape, and poor feeding. Neurologic features become more apparent in early childhood and progress slowly.</p><p><b>Early developmental milestones.</b> In the Old Order Amish, <a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al [2004]</a> reported that the presenting feature in most individuals was a delay in reaching early gross motor and speech and language milestones (walking and talking) compared to unaffected sibs. Twenty of the 21 individuals were delayed in walking (age range 12-22 months; mean age 16.1 months). The age at which they started talking ranged from seven to 36 months, with a mean age of 17.5 months. In those whose milestones were not noticeably delayed, the character of the gait and/or speech was the first abnormality reported.</p><p><b>Neurologic features.</b> Troyer syndrome leads to gait ataxia and progressive spastic paraparesis that typically develops during childhood. Lower-limb distal tendon reflexes are increased. Distal weakness, when present, is mild and disproportionate to the observed spasticity. Distal amyotrophy was found in all individuals older than age 13 years and also in one child age seven years reported by <a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al [2004]</a>. In the more severely affected, generally older, individuals, weakness of the small hand muscles was observed. Most individuals had mild weakness of the abductor pollicis brevis, abductor digiti minimi, and palmar and dorsal interossei. More proximal upper-limb strength is preserved. The most severely affected individuals had choreoathetoid movements (i.e., an irregular, constant succession of slow, spasmodic writhing with involuntary flexion, extension, pronation, and supination) of the fingers and hands, and sometimes the toes and feet. Difficulty with walking increased with age; affected individuals generally became wheelchair bound during the sixth to seventh decade of life.</p><p>Progressive spastic dysarthria is reported with brisk jaw jerk, often accompanied by slow, spastic tongue movements. Excessive drooling is commonly observed in childhood and persists into adulthood in the most severely affected individuals.</p><p>Microcephaly and macrocephaly have both been reported [<a class="bibr" href="#spg20.REF.patel.2002.347" rid="spg20.REF.patel.2002.347">Patel et al 2002</a>, <a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>, <a class="bibr" href="#spg20.REF.manzini.2010.516" rid="spg20.REF.manzini.2010.516">Manzini et al 2010</a>, <a class="bibr" href="#spg20.REF.tawamie.2015.315" rid="spg20.REF.tawamie.2015.315">Tawamie et al 2015</a>, <a class="bibr" href="#spg20.REF.butler.2016.1780" rid="spg20.REF.butler.2016.1780">Butler et al 2016</a>, <a class="bibr" href="#spg20.REF.dardour.2017" rid="spg20.REF.dardour.2017">Dardour et al 2017</a>, <a class="bibr" href="#spg20.REF.spiegel.2017.55" rid="spg20.REF.spiegel.2017.55">Spiegel et al 2017</a>].</p><p><b>Learning difficulties</b> were reported in all but one affected individual of Amish descent. Most were able to complete eighth grade, the traditional end point of Amish education. In all but one individual, school performance was significantly worse than that of unaffected sibs. Most affected individuals had persistent cognitive deficits. Two individuals completed high school and worked for several years [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>].</p><p><b>Emotional lability and affective disorders</b> including inappropriate euphoria and/or crying are common [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>, <a class="bibr" href="#spg20.REF.tawamie.2015.315" rid="spg20.REF.tawamie.2015.315">Tawamie et al 2015</a>].</p><p><b>Skeletal abnormalities</b> described in individuals with Troyer syndrome include the following:</p><ul><li class="half_rhythm"><div>Short stature when compared to parents and/or sibs [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>]</div></li><li class="half_rhythm"><div>Overgrowth of the maxilla leading to overbite (5/6 individuals) [<a class="bibr" href="#spg20.REF.manzini.2010.516" rid="spg20.REF.manzini.2010.516">Manzini et al 2010</a>]</div></li><li class="half_rhythm"><div>Small feet with <i>pes cavus</i> (17/21 individuals) [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>]</div></li><li class="half_rhythm"><div>"Hammer toes" in the most severely affected individuals [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>]</div></li><li class="half_rhythm"><div>Hyperextensible proximal interphalangeal joints of the fingers (8/21) [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>]</div></li><li class="half_rhythm"><div>Brachydactyly (5/6 individuals), clinodactyly, camptodactyly, and hypoplastic fifth middle phalanges [<a class="bibr" href="#spg20.REF.manzini.2010.516" rid="spg20.REF.manzini.2010.516">Manzini et al 2010</a>]</div></li><li class="half_rhythm"><div>Mild knee valgus (4/21) [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>]</div></li><li class="half_rhythm"><div>Mild kyphoscoliosis has been reported but radiographic correlation was not available [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>]</div></li></ul><p><b>Life expectancy</b> is normal.</p><p><b>Neuroimaging.</b> White-matter hyperintensities described include periventricular white-matter hyperintensity on T<sub>2</sub>-weighted images reported in eight individuals [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>, <a class="bibr" href="#spg20.REF.manzini.2010.516" rid="spg20.REF.manzini.2010.516">Manzini et al 2010</a>, <a class="bibr" href="#spg20.REF.dardour.2017" rid="spg20.REF.dardour.2017">Dardour et al 2017</a>] and increased T<sub>2</sub>/FLAIR signal within the ventrolateral thalami and posterior limb of the internal capsule reported in one individual [<a class="bibr" href="#spg20.REF.butler.2016.1780" rid="spg20.REF.butler.2016.1780">Butler et al 2016</a>]. The white-matter abnormalities described are not specific to Troyer syndrome and can be present in other forms of hereditary spastic paraplegia.</p><p><b>Nerve conduction studies</b> performed in two individuals who were not severely affected were normal in the right upper and lower limb. In one of these individuals, electromyography (EMG) was normal bilaterally except for a polyphasic potential in the medial head of the gastrocnemius on one side. In the other individual, EMG of the right upper and lower limb was normal [<a class="bibr" href="#spg20.REF.proukakis.2004.1105" rid="spg20.REF.proukakis.2004.1105">Proukakis et al 2004</a>].</p></div><div id="spg20.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations have been observed.</p></div><div id="spg20.Prevalence"><h3>Prevalence</h3><p>The prevalence is unknown. A previous study documented 21 individuals with Troyer syndrome in a population of approximately 50,000 Amish [<a class="bibr" href="#spg20.REF.patel.2002.347" rid="spg20.REF.patel.2002.347">Patel et al 2002</a>]. To date the <a href="/books/NBK1382/table/spg20.T.spart_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobspg20Tspartpathogenicvariantsdiscus">c.1110delA</a> variant has not been observed outside of the Old Order Amish population.</p><p>Troyer syndrome has now been reported in several additional individuals worldwide.</p></div></div><div id="spg20.Genetically_Related_Disorders"><h2 id="_spg20_Genetically_Related_Disorders_">Genetically Related 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>SPART</i>.</p></div><div id="spg20.Differential_Diagnosis"><h2 id="_spg20_Differential_Diagnosis_">Differential Diagnosis</h2><p>See <a href="/books/n/gene/hsp/?report=reader">Hereditary Spastic Paraplegia Overview</a> for a review.</p><p>Troyer syndrome shares some features with <a href="/books/n/gene/arsacs/?report=reader">ARSACS</a> (<i>a</i>utosomal <i>r</i>ecessive <i>s</i>pastic <i>a</i>taxia of <i>C</i>harlevoix-<i>S</i>aguenay); however, nystagmus, abnormalities of ocular movement, and mitral valve prolapse are not features of Troyer syndrome.</p><p>Some Amish children/infants have been diagnosed with <a href="/books/n/gene/rss/?report=reader">Silver-Russell syndrome</a> due to low birth weight, relatively preserved head circumference, triangular face shape, and short stature; however, spastic paraplegia, a consistent feature of Troyer syndrome, is not seen in individuals with Silver-Russell syndrome.</p></div><div id="spg20.Management"><h2 id="_spg20_Management_">Management</h2><div id="spg20.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs of an individual diagnosed with Troyer syndrome, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:</p><ul><li class="half_rhythm"><div>Growth assessment including height, weight, and head circumference</div></li><li class="half_rhythm"><div>Consultation with a neurologist and examination to identify features of Troyer syndrome with attention to evidence of pyramidal and/or extrapyramidal movement disorders, distal amyotrophy, hyperreflexia, swallowing difficulties</div></li><li class="half_rhythm"><div>Developmental assessment with attention to gross motor and fine motor skills, as well as speech and language development, looking for possible dysarthria and tongue dyspraxia</div></li><li class="half_rhythm"><div>Psychological assessment, with attention to presence or absence of emotional lability</div></li><li class="half_rhythm"><div>Physical examination for skeletal abnormalities and x-ray examination for kyphoscoliosis as needed</div></li><li class="half_rhythm"><div>Consultation with a clinical geneticist and/or genetic counselor</div></li></ul></div><div id="spg20.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>No specific treatment to prevent or reverse the neurologic degeneration in Troyer syndrome currently exists. Treatments are directed at reducing symptoms, maintaining mobility, and improving balance, strength, and agility. Individuals should be evaluated periodically (annually or as needed) by a neurologist, physiatrist, occupational therapist, and speech and language therapist to assess progression and develop treatment strategies to maximize walking ability and reduce symptoms.</p><ul><li class="half_rhythm"><div>Daily physical therapy regimen directed toward maintaining and improving cardiovascular health, muscle strength, and gait and reducing spasticity. These recommendations are based on the experience of approximately 200 persons with hereditary spastic paraplegia, who nearly unanimously reported benefit from daily physical exercise [<a class="bibr" href="#spg20.REF.fink.2003.s106" rid="spg20.REF.fink.2003.s106">Fink 2003</a>].</div></li><li class="half_rhythm"><div>Occupational therapy, assistive walking devices, and ankle-foot orthotics as required</div></li><li class="half_rhythm"><div>Speech and language therapy to improve/maintain speech and swallowing, and communication devices as required</div></li><li class="half_rhythm"><div>Medication to reduce drooling may be helpful.</div></li><li class="half_rhythm"><div>Medications to reduce muscle spasticity (e.g., Lioresal<sup>®</sup> [oral or intrathecal]). Dosages need to be individualized as some individuals have weakness with less spasticity (and thus do not benefit from large doses), while others have significant spasticity and require high doses. Tizanidine, dantrolene (see <a href="#spg20.AgentsCircumstances_to_Avoid">Agents/Circumstances to Avoid</a>), and botulinum A and B toxin injections (Botox<sup>®</sup>, Dysport<sup>®</sup>, Xeomin<sup>®</sup>, or Myobloc<sup>®</sup>) have also been useful in reducing muscle spasticity.</div></li><li class="half_rhythm"><div>Medications to reduce urinary urgency (e.g., oxybutynin, solifenacin, mirabegron, intrabladder injections with Botox<sup>®</sup>)</div></li><li class="half_rhythm"><div>Antidepressants or mood stabilizers to manage emotional lability</div></li></ul><p>See also <a href="/books/n/gene/hsp/?report=reader">Hereditary Spastic Paraplegia Overview</a>.</p></div><div id="spg20.Surveillance"><h3>Surveillance</h3><p>The following are appropriate:</p><ul><li class="half_rhythm"><div>Evaluation with a neurologist every six to 12 months (or as required depending on age and severity) to review symptoms, assess need for multidisciplinary input, and update medications</div></li><li class="half_rhythm"><div>Monitor for dysphagia to reduce risk of aspiration</div></li><li class="half_rhythm"><div>Psychiatric/psychological assessment as indicated</div></li><li class="half_rhythm"><div>Developmental assessment / cognitive testing as indicated depending on age and severity</div></li><li class="half_rhythm"><div>Annual assessment of orthopedic manifestations</div></li></ul></div><div id="spg20.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Dantrolene should be avoided in persons who are ambulatory as it may induce irreversible weakness, which can adversely interfere with overall mobility.</p></div><div id="spg20.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#spg20.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="spg20.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 information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="spg20.Genetic_Counseling"><h2 id="_spg20_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="spg20.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Troyer syndrome is inherited in an autosomal recessive manner.</p></div><div id="spg20.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>The parents of an affected individual are obligate heterozygotes (i.e., carriers of one <i>SPART</i> pathogenic variant).</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>At conception, the sibs of an affected individual have a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> To date, individuals with Troyer syndrome are not known to reproduce [Patel & Crosby, personal observation].</p><p><b>Other family members.</b> Each sib of the proband's parents is at 50% risk of being a carrier of a <i>SPART</i> pathogenic variant.</p></div><div id="spg20.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>SPART</i> pathogenic variants in the family.</p></div><div id="spg20.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><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, clarification of carrier status, 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 carriers or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown).</p></div><div id="spg20.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SPART</i> pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for Troyer syndrome are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. 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="spg20.Resources"><h2 id="_spg20_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>National Institute of Neurological Disorders and Stroke (NINDS)</b>
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</div><div>
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<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Hereditary-Spastic-Paraplegia-Information-Page" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hereditary Spastic Paraplegia</a>
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</div></li><li class="half_rhythm"><div>
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<b>Spastic Paraplegia Foundation, Inc.</b>
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</div><div><b>Phone:</b> 877-773-4483</div><div><b>Email:</b> information@sp-foundation.org</div><div>
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<a href="http://sp-foundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">sp-foundation.org</a>
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</div></li></ul>
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</div><div id="spg20.Molecular_Genetics"><h2 id="_spg20_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="figspg20molgenTA"><a href="/books/NBK1382/table/spg20.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobspg20molgenTA"><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="spg20.molgen.TA"><a href="/books/NBK1382/table/spg20.molgen.TA/?report=objectonly" target="object" rid-ob="figobspg20molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Troyer Syndrome: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figspg20molgenTB"><a href="/books/NBK1382/table/spg20.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobspg20molgenTB"><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="spg20.molgen.TB"><a href="/books/NBK1382/table/spg20.molgen.TB/?report=objectonly" target="object" rid-ob="figobspg20molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Troyer Syndrome (View All in OMIM) </p></div></div><div id="spg20.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The pathogenic basis of Troyer syndrome is currently unclear.</p><p><b>Gene structure.</b>
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<i>SPART</i> (formerly <i>SPG20</i>) resides within 731 kb and comprises nine exons. Multiple alternatively spliced variants, encoding the same protein, have been identified; the longest transcript is <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_015087.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_015087.5</a>. For a detailed summary of gene and protein information, see <a href="/books/NBK1382/?report=reader#spg20.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> Four pathogenic <i>SPART</i> variants have been identified to date: c.1110delA in exon 4 in an extended Old Order Amish pedigree [<a class="bibr" href="#spg20.REF.patel.2002.347" rid="spg20.REF.patel.2002.347">Patel et al 2002</a>], a recurrent homozygous 2-nucleotide deletion c.364_365delAT p.(Met122ValfsTer2) in Omani, Turkish, and Filipino families [<a class="bibr" href="#spg20.REF.manzini.2010.516" rid="spg20.REF.manzini.2010.516">Manzini et al 2010</a>, <a class="bibr" href="#spg20.REF.tawamie.2015.315" rid="spg20.REF.tawamie.2015.315">Tawamie et al 2015</a>, <a class="bibr" href="#spg20.REF.butler.2016.1780" rid="spg20.REF.butler.2016.1780">Butler et al 2016</a>], a homozygous nonsense variant c.1369C>T (p.Arg457Ter) in a Moroccan family [<a class="bibr" href="#spg20.REF.dardour.2017" rid="spg20.REF.dardour.2017">Dardour et al 2017</a>], and a homozygous 1-nucleotide substitution c.988A>G (p.Met330Val) in an Israeli-Arab child [<a class="bibr" href="#spg20.REF.spiegel.2017.55" rid="spg20.REF.spiegel.2017.55">Spiegel et al 2017</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figspg20Tspartpathogenicvariantsdiscus"><a href="/books/NBK1382/table/spg20.T.spart_pathogenic_variants_discus/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobspg20Tspartpathogenicvariantsdiscus"><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="spg20.T.spart_pathogenic_variants_discus"><a href="/books/NBK1382/table/spg20.T.spart_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figobspg20Tspartpathogenicvariantsdiscus">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>SPART</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
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<i>SPART</i> (formerly <i>SPG20</i>) is widely expressed in adult and fetal human tissues. It encodes a 666-amino acid protein named spartin (spastic paraplegia autosomal recessive Troyer syndrome). Spartin possesses a MIT domain (contained within microtubule-interacting and trafficking molecules) [<a class="bibr" href="#spg20.REF.ciccarelli.2003.437" rid="spg20.REF.ciccarelli.2003.437">Ciccarelli et al 2003</a>] as does spastin, which is encoded by <i>SPAST</i>, the most commonly mutated gene in hereditary spastic paraplegia, accounting for approximately 40% of autosomal dominant cases [<a class="bibr" href="#spg20.REF.hazan.1999.296" rid="spg20.REF.hazan.1999.296">Hazan et al 1999</a>] (see <a href="/books/n/gene/spg4/?report=reader">Spastic Paraplegia Type 4</a>). The identification of the same domain in spastin and spartin suggests related functionality of these proteins.</p><p>Spartin, a cytosolic and membrane-associated protein that interacts with EPS15, an endocytic and trafficking protein, may have a number of roles, including functioning at endosomes and in droplet formation [<a class="bibr" href="#spg20.REF.bakowska.2005.1042" rid="spg20.REF.bakowska.2005.1042">Bakowska et al 2005</a>]. SPG20 associates with the surface of lipid droplets (LDs), regulating their size and number. SPG20 binds to another LD protein, TIP47; both proteins compete with an additional LD protein, adipophilin/adipocyte differentiation-related protein. Spartin may also be involved in endocytosis and vesicle trafficking [<a class="bibr" href="#spg20.REF.bakowska.2005.1042" rid="spg20.REF.bakowska.2005.1042">Bakowska et al 2005</a>].</p><p><b>Abnormal gene product.</b> Troyer syndrome is most likely caused by loss of function of spartin, as would be expected with an autosomal recessive disorder. A full explanation for the disease will require an understanding of the normal functions of spartin and the relevance of each function to axonal biology [<a class="bibr" href="#spg20.REF.edwards.2009.31" rid="spg20.REF.edwards.2009.31">Edwards et al 2009</a>].</p></div></div><div id="spg20.Chapter_Notes"><h2 id="_spg20_Chapter_Notes_">Chapter Notes</h2><div id="spg20.Author_History"><h3>Author History</h3><p>Emma Baple, MBBS, MRCPCH, PhD (2019-present)<br />Andrew Crosby, PhD (2004-present)<br />Gaurav Harlalka, MRes; University of London (2011-2019)<br />Heema Patel, PhD; University of London (2004-2019)</p></div><div id="spg20.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>6 June 2019 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 August 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>16 November 2004 (me) Review posted live</div></li><li class="half_rhythm"><div>11 August 2004 (ac) Original submission</div></li></ul></div></div><div id="spg20.References"><h2 id="_spg20_References_">References</h2><div id="spg20.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.bakowska.2005.1042">Bakowska JC, Jenkins R, Pendleton J, Blackstone C. The Troyer syndrome (SPG20) protein spartin interacts with Eps15. <span><span class="ref-journal">Biochem Biophys Res Commun. </span>2005;<span class="ref-vol">334</span>:1042–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16036216" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16036216</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.butler.2016.1780">Butler S, Helbig KL, Alcaraz W, Seaver LH, Hsieh DT, Rohena L. Three cases of Troyer syndrome in two families of Filipino descent. <span><span class="ref-journal">Am J Med Genet A. </span>2016;<span class="ref-vol">170</span>:1780–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27112432" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27112432</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.ciccarelli.2003.437">Ciccarelli FD, Proukakis C, Patel H, Cross H, Azam S, Patton MA, Bork P, Crosby AH. The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. <span><span class="ref-journal">Genomics. </span>2003;<span class="ref-vol">81</span>:437–41.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12676568" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12676568</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.dardour.2017">Dardour L, Roelens F, Race V, Souche E, Holvoet M, Devriendt K. SPG20 mutation in three siblings with familial hereditary spastic paraplegia. <span><span class="ref-journal">Cold Spring Harb Mol Case Stud. </span>2017;<span class="ref-vol">3</span>(4)</span> [<a href="/pmc/articles/PMC5495031/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5495031</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28679690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28679690</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.edwards.2009.31">Edwards TL, Clowes VE, Tsang HTH, Connell JW, Sanderson CM, Luzio JP, Reid E. Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5. <span><span class="ref-journal">Biochem J. </span>2009;<span class="ref-vol">423</span>:31–9.</span> [<a href="/pmc/articles/PMC2762690/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2762690</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19580544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19580544</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.fink.2003.s106">Fink JK. Advances in hereditary spastic paraplegias. <span><span class="ref-journal">Exp Neurol. </span>2003;<span class="ref-vol">184</span>:S106–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14597333" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14597333</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.hazan.1999.296">Hazan J, Fonknechten N, Mavel D, Paternotte C, Samson D, Artiguenave F, Davoine CS, Cruaud C, Durr A, Wincker P, Brottier P, Cattolico L, Barbe V, Burgunder JM, Prud'homme JF, Brice A, Fontaine B, Heilig B, Weissenbach J. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. <span><span class="ref-journal">Nat Genet. </span>1999;<span class="ref-vol">23</span>:296–303.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10610178" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10610178</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.manzini.2010.516">Manzini MC, Rajab A, Maynard TM, Mochida GH, Tan W, Nasir R, Hill RS, Gleason D, Al Saffar M, Partlow JN, Barry BJ, Vernon M, LaMantia A, Walsh CA. Developmental and degenerative features in a complicated spastic paraplegia. <span><span class="ref-journal">Ann Neurol. </span>2010;<span class="ref-vol">67</span>:516–25.</span> [<a href="/pmc/articles/PMC3027847/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3027847</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20437587" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20437587</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.patel.2002.347">Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH. SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. <span><span class="ref-journal">Nat Genet. </span>2002;<span class="ref-vol">31</span>:347–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12134148" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12134148</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.proukakis.2004.1105">Proukakis C, Cross H, Patel H, Patton MA, Valentine A, Crosby AH. Troyer syndrome revisited. A clinical and radiological study of a complicated hereditary spastic paraplegia. <span><span class="ref-journal">J Neurol. </span>2004;<span class="ref-vol">251</span>:1105–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15372254" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15372254</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.spiegel.2017.55">Spiegel R, Soiferman D, Shaag A, Shalev S, Elpeleg O, Saada A. Novel homozygous missense mutation in SPG20 gene results in Troyer syndrome associated with mitochondrial cytochrome c oxidase deficiency. <span><span class="ref-journal">JIMD Rep. </span>2017;<span class="ref-vol">33</span>:55–60.</span> [<a href="/pmc/articles/PMC5413448/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5413448</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27539578" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27539578</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="spg20.REF.tawamie.2015.315">Tawamie H, Wohlleber E, Uebe S, Schmäl C, Nöthen MM, Abou Jamra R. Recurrent null mutation in SPG20 leads to Troyer syndrome. <span><span class="ref-journal">Mol Cell Probes. </span>2015;<span class="ref-vol">29</span>:315–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26003402" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26003402</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1382_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Emma Baple</span>, MBBS, MRCPCH, PhD<div class="affiliation small">Medical Research
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Research, Innovation, Learning and Development
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Wellcome Wolfson Centre
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University of Exeter Medical School
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Exeter, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.retexe@elpab.e" class="oemail">ku.ca.retexe@elpab.e</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Andrew Crosby</span>, PhD<div class="affiliation small">Medical Research
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Research, Innovation, Learning and Development
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Wellcome Wolfson Centre
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University of Exeter Medical School
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Exeter, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.retexe@ybsorc.h.a" class="oemail">ku.ca.retexe@ybsorc.h.a</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">November 16, 2004</span>; Last Update: <span itemprop="dateModified">June 6, 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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hereby granted to reproduce, distribute, and translate copies of content materials for
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noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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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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Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
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of GeneReviews chapters for use in lab reports and clinic notes are a permitted
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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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Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
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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>Baple E, Crosby A. Troyer Syndrome. 2004 Nov 16 [Updated 2019 Jun 6]. 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/tps/?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/tuberous-sclerosis/?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="figobspg20Tmoleculargenetictestingusedi"><div id="spg20.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 Troyer Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1382/table/spg20.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__spg20.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_spg20.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_spg20.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_spg20.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 Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_spg20.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>SPART</i>
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</td><td headers="hd_h_spg20.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_spg20.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td></tr><tr><td headers="hd_h_spg20.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>4</sup></td><td headers="hd_h_spg20.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown, none reported</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="spg20.TF.1.1"><p class="no_margin">See <a href="/books/NBK1382/?report=reader#spg20.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="spg20.TF.1.2"><p class="no_margin">See <a href="#spg20.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="spg20.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="spg20.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as 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></div></div></div></article><article data-type="table-wrap" id="figobspg20molgenTA"><div id="spg20.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Troyer Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1382/table/spg20.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__spg20.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_spg20.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_spg20.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_spg20.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_spg20.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_spg20.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_spg20.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_spg20.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/23111" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>SPART</i>
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</a>
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</td><td headers="hd_b_spg20.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=23111" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">13q13<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_b_spg20.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/Q8N0X7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Spartin</a>
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</td><td headers="hd_b_spg20.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/SPG20" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SPG20 database</a>
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</td><td headers="hd_b_spg20.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=SPART" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SPART</a>
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</td><td headers="hd_b_spg20.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=SPART[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SPART</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="spg20.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="figobspg20molgenTB"><div id="spg20.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Troyer Syndrome (<a href="/omim/275900,607111" 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/NBK1382/table/spg20.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__spg20.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/275900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">275900</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPASTIC PARAPLEGIA 20, AUTOSOMAL RECESSIVE; SPG20</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/607111" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607111</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPARTIN; SPART</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobspg20Tspartpathogenicvariantsdiscus"><div id="spg20.T.spart_pathogenic_variants_discus" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>SPART</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1382/table/spg20.T.spart_pathogenic_variants_discus/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__spg20.T.spart_pathogenic_variants_discus_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.988A>G</td><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Met330Val</td><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_015087.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_015087<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_055902.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_055902<wbr style="display:inline-block"></wbr>​.1</a>
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</td></tr><tr><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1369C>T</td><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg457Ter</td></tr><tr><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1110delA</td><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Lys370AsnfsTer30<br />(fs369-398Ter399)</td></tr><tr><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.364_365delAT</td><td headers="hd_h_spg20.T.spart_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Met122ValfsTer2<br />(M122V_C123Ter)</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="spg20.TF.2.1"><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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