Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion
- PMID: 19105190
- DOI: 10.1002/humu.20945
Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion
Abstract
Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing.
2008 Wiley-Liss, Inc.
Similar articles
-
Expanding the clinical spectrum of SPG11 gene mutations in recessive hereditary spastic paraplegia with thin corpus callosum.Eur J Med Genet. 2011 Jan-Feb;54(1):82-5. doi: 10.1016/j.ejmg.2010.10.006. Epub 2010 Nov 12. Eur J Med Genet. 2011. PMID: 20971220 Free PMC article.
-
Novel mutations of the SPG11 gene in hereditary spastic paraplegia with thin corpus callosum.J Neurol Sci. 2008 Dec 15;275(1-2):92-9. doi: 10.1016/j.jns.2008.07.038. Epub 2008 Oct 2. J Neurol Sci. 2008. PMID: 18835492
-
A case report of SPG11 mutations in a Chinese ARHSP-TCC family.BMC Neurol. 2016 Jun 3;16:87. doi: 10.1186/s12883-016-0604-5. BMC Neurol. 2016. PMID: 27256065 Free PMC article.
-
[Recent advances of study on hereditary spastic paraplegia type 11].Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009 Dec;26(6):670-3. doi: 10.3760/cma.j.issn.1003-9406.2009.06.013. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009. PMID: 19953491 Review. Chinese.
-
SPG11: clinical and genetic features of seven Czech patients and literature review.Neurol Res. 2022 May;44(5):379-389. doi: 10.1080/01616412.2021.1975224. Epub 2022 Mar 7. Neurol Res. 2022. PMID: 35254204 Review.
Cited by
-
Chinese families with autosomal recessive hereditary spastic paraplegia caused by mutations in SPG11.BMC Neurol. 2020 Jan 3;20(1):2. doi: 10.1186/s12883-019-1593-y. BMC Neurol. 2020. PMID: 31900114 Free PMC article.
-
Whole-genome sequencing of two probands with hereditary spastic paraplegia reveals novel splice-donor region variant and known pathogenic variant in SPG11.Cold Spring Harb Mol Case Stud. 2016 Nov;2(6):a001248. doi: 10.1101/mcs.a001248. Cold Spring Harb Mol Case Stud. 2016. PMID: 27900367 Free PMC article.
-
An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions.BMC Neurol. 2022 Jan 3;22(1):2. doi: 10.1186/s12883-021-02514-z. BMC Neurol. 2022. PMID: 34979968 Free PMC article.
-
Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease.Hum Mol Genet. 2015 Sep 1;24(17):4984-96. doi: 10.1093/hmg/ddv220. Epub 2015 Jun 17. Hum Mol Genet. 2015. PMID: 26085577 Free PMC article.
-
SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.Brain. 2010 Feb;133(Pt 2):591-8. doi: 10.1093/brain/awp325. Epub 2010 Jan 28. Brain. 2010. PMID: 20110243 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
