Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10
Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower extremities. Only a few different mutations in the SPG10 gene, KIF5A, have been described in pure dominant forms of the disease. We sequenc...
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Published in | Human mutation Vol. 30; no. 2; pp. E376 - E385 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.02.2009
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Subjects | |
Online Access | Get full text |
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Summary: | Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower extremities. Only a few different mutations in the SPG10 gene, KIF5A, have been described in pure dominant forms of the disease. We sequenced the motor domain of KIF5A in a large panel of 205 European HSP patients with either pure or complicated forms of the disease. We identified eight different heterozygous missense mutations, seven novels, in eight different families of French origin. Residue R280 was a mutational hot spot. Interestingly, the patients in 7/8 families had a complex phenotype, with peripheral neuropathy, severe upper limb amyotrophy (Silver syndrome-like), mental impairment, parkinsonism, deafness and/or retinitis pigmentosa as variably associated features. We report the largest series of SPG10 families described so far, which extends both the mutational spectrum of the disease and its phenotype, which now includes complicated forms of HSP. SPG10 mutations were found in 10% of our complicated forms of HSP, suggesting that mutations in KIF5A represent the major cause of complicated AD-HSP in France. |
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Bibliography: | http://dx.doi.org/10.1002/humu.20920 This work was supported financially by the Programme Hospitalier de Recherche Clinique (to AD), INSERM, the E-Rare EUROSPA network (to A.Br.) and the VERUM foundation (to A.Br.). C.G. received grants from the Centre Hospitalier Universitaire de Bordeaux. A.Bo. received a fellowship from the French Association Strümpell-Lorrain (ASL-France). istex:206FB1D1E305CD73E4290284D43A3320889C760D Communicated by Mireille Claustres ark:/67375/WNG-TFQ0B8MJ-J ArticleID:HUMU20920 These authors contributed equally to the work ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1059-7794 1098-1004 |
DOI: | 10.1002/humu.20920 |