Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia (ADCA) of which the mutation causing the disease has recently been characterised as an expanded CAG trinucleotide repeat in the gene coding for the alpha1A-subunit of the voltage dependent calcium channel.
The aim was to further characterise the SCA6 phenotype Methods-The SCA6 mutation was investigated in 69 German families with ADCA and 61 patients with idiopathic sporadic cerebellar ataxia and the CAG repeat length of the expanded allele was correlated with the disease phenotype.
Expanded alleles were found in nine of 69 families as well as in four patients with sporadic disease.
Disease onset ranged from 30 to 71 years of age and was significantly later than in other forms of ADCA.
Age at onset correlated inversely with repeat length.
The SCA6 phenotype comprises predominantly cerebellar signs in concordance with isolated cerebellar atrophy on MRI.
Non-cerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism.
Neither these clinical signs nor progression rate correlated with CAG repeat length.
Conclusions-This study provides the first detailed characterisation of the SCA6 phenotype.
Clinical features apart from cerebellar signs were highly variable in patients with SCA6.
By comparison with SCA1, SCA2, and SCA3 no clinical or electrophysiological finding was specific for SCA6. (...)
Mots-clés Pascal : Caractère autosomique, Caractère dominant, Type, Mutation, Gène, Trinucléotide, Canal ionique, Calcium, Phénotype, Allemand, Génotype, Sporadique, Idiopathique, Etude comparative, Déterminisme génétique, Diagnostic, Etude familiale, Homme, Maladie héréditaire, Système nerveux pathologie, Système nerveux central pathologie, Encéphale pathologie, Moelle épinière pathologie, Maladie dégénérative, Ataxie spinocérébelleuse
Mots-clés Pascal anglais : Autosomal character, Dominant character, Type, Mutation, Gene, Trinucleotide, Ionic channel, Calcium, Phenotype, German, Genotype, Sporadic, Idiopathic, Comparative study, Genetic determinism, Diagnosis, Family study, Human, Genetic disease, Nervous system diseases, Central nervous system disease, Cerebral disorder, Spinal cord disease, Degenerative disease, Spinocerebellar ataxia
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0074475
Code Inist : 002B17G. Création : 14/05/1998.