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Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)

BACKGROUND: Mutations in the SPG4 gene (spastin) and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP). Recently, mutations in the REEP1 gene were identified to cause autosomal dominant HSP type SPG31. The purpose...

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Autores principales: Schlang, Katharina J, Arning, Larissa, Epplen, Joerg T, Stemmler, Susanne
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492855/
https://www.ncbi.nlm.nih.gov/pubmed/18644145
http://dx.doi.org/10.1186/1471-2350-9-71
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author Schlang, Katharina J
Arning, Larissa
Epplen, Joerg T
Stemmler, Susanne
author_facet Schlang, Katharina J
Arning, Larissa
Epplen, Joerg T
Stemmler, Susanne
author_sort Schlang, Katharina J
collection PubMed
description BACKGROUND: Mutations in the SPG4 gene (spastin) and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP). Recently, mutations in the REEP1 gene were identified to cause autosomal dominant HSP type SPG31. The purpose of this study was to determine the prevalence of REEP1 mutations in a cohort of 162 unrelated Caucasian index patients with 'pure' HSP and a positive family history (at least two persons per family presented symptoms). METHODS: 162 patients were screened for mutations by, both, DHPLC and direct sequencing. RESULTS: Ten mutations were identified in the REEP1 gene, these included eight novel mutations comprising small insertions/deletions causing frame shifts and subsequently premature stop codons, one nonsense mutation and one splice site mutation as well as two missense mutations. Both missense mutations and the splice site mutation were not identified in 170 control subjects. CONCLUSION: In our HSP cohort we found pathogenic mutations in 4.3% of cases with autosomal dominant inheritance. Our results confirm the previously observed mutation range of 3% to 6.5%, respectively, and they widen the spectrum of REEP1 mutations.
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spelling pubmed-24928552008-08-01 Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31) Schlang, Katharina J Arning, Larissa Epplen, Joerg T Stemmler, Susanne BMC Med Genet Research Article BACKGROUND: Mutations in the SPG4 gene (spastin) and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP). Recently, mutations in the REEP1 gene were identified to cause autosomal dominant HSP type SPG31. The purpose of this study was to determine the prevalence of REEP1 mutations in a cohort of 162 unrelated Caucasian index patients with 'pure' HSP and a positive family history (at least two persons per family presented symptoms). METHODS: 162 patients were screened for mutations by, both, DHPLC and direct sequencing. RESULTS: Ten mutations were identified in the REEP1 gene, these included eight novel mutations comprising small insertions/deletions causing frame shifts and subsequently premature stop codons, one nonsense mutation and one splice site mutation as well as two missense mutations. Both missense mutations and the splice site mutation were not identified in 170 control subjects. CONCLUSION: In our HSP cohort we found pathogenic mutations in 4.3% of cases with autosomal dominant inheritance. Our results confirm the previously observed mutation range of 3% to 6.5%, respectively, and they widen the spectrum of REEP1 mutations. BioMed Central 2008-07-21 /pmc/articles/PMC2492855/ /pubmed/18644145 http://dx.doi.org/10.1186/1471-2350-9-71 Text en Copyright © 2008 Schlang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Schlang, Katharina J
Arning, Larissa
Epplen, Joerg T
Stemmler, Susanne
Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
title Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
title_full Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
title_fullStr Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
title_full_unstemmed Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
title_short Autosomal dominant hereditary spastic paraplegia: Novel mutations in the REEP1 gene (SPG31)
title_sort autosomal dominant hereditary spastic paraplegia: novel mutations in the reep1 gene (spg31)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492855/
https://www.ncbi.nlm.nih.gov/pubmed/18644145
http://dx.doi.org/10.1186/1471-2350-9-71
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