Analysis of the SCAI CAG repeat in a large number of families with dominant ataxia: Clinical and molecular correlations

✍ Scribed by O. Dubourg; A. Dürr; G. Cancel; G. Stevanin; C. Penet; Y. Agid; A. Brice; H. Chneiweiss

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 494 KB
• Volume: 37
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.410370207

✦ Synopsis

Autosomal dominantly inherited ataxias are a clinically and genetically heterogeneous group of neurodegenerative disorders. The gene involved in one subtype, spinocerebellar ataxia 1 (SCA l), was first localized to chromosome 6p. An unstable CAG repeat has been identified as the responsible mutation. In this study, 88 families with various types of inherited acaxias and 16 individuals with sporadic cerebellar ataxia were investigated to determine the frequency of this mutation, the behavior of the SCAl CAG repeat during transmission, and the clinical features specific to this form of disease. Only 12 of the families carried the SCAl mutation; 10 of the 12 were of French origin. When transmitted paternally. the repeat was more unstable and larger in size. Age at onset was inversely correlated with the number of CAG repeats. Anticipation in age at onset of about 11 years was observed in offspring. Analysis of the clinical features did not distinguish SCAl from other forms of dominantly inherited ataxias. In the absence of distinguishing clinical characteristics, the diagnosis of SCAl in single affected patients or family members can only be made by direct detection of the mutation, opening the way for presymptomatic testing.