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Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10
Author(s) -
Goizet Cyril,
Boukhris Amir,
Mundwiller Emeline,
Tallaksen Chantal,
Forlani Sylvie,
Toutain Annick,
Carriere Nathalie,
Paquis Véronique,
Depienne Christel,
Durr Alexandra,
Stevanin Giovanni,
Brice Alexis
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20920
Subject(s) - hereditary spastic paraplegia , missense mutation , biology , genetics , phenotype , retinitis pigmentosa , spasticity , disease , parkinsonism , genetic heterogeneity , mutation , gene , medicine , physical medicine and rehabilitation
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. © 2008 Wiley‐Liss, Inc.