Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10.
Hum. Mutat.. 2009-02-01; 30(2): E376-E385
DOI: 10.1002/humu.20920
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1. Hum Mutat. 2009 Feb;30(2):E376-85. doi: 10.1002/humu.20920.
Complicated forms of autosomal dominant hereditary spastic paraplegia are
frequent in SPG10.
Goizet C(1), Boukhris A, Mundwiller E, Tallaksen C, Forlani S, Toutain A,
Carriere N, Paquis V, Depienne C, Durr A, Stevanin G, Brice A.
Author information:
(1)INSERM, UMR_S679, Paris, France.
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.
(c) 2008 Wiley-Liss, Inc.
DOI: 10.1002/humu.20920
PMID: 18853458 [Indexed for MEDLINE]