Analysis of the SCA1 CAG repeat in a large number of families with dominant ataxia: clinical and molecular correlations.
Ann Neurol.. 1995-02-01; 37(2): 176-180
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1. Ann Neurol. 1995 Feb;37(2):176-80.
Analysis of the SCA1 CAG repeat in a large number of families with dominant
ataxia: clinical and molecular correlations.
Dubourg O(1), Dürr A, Cancel G, Stevanin G, Chneiweiss H, Penet C, Agid Y, Brice
(1)INSERM U 289, Hôpital de la Salpêtrière, Paris, France.
Autosomal dominantly inherited ataxias are a clinically and genetically
heterogeneous group of neurodegenerative disorders. The gene involved in one
subtype, spinocerebellar ataxia 1 (SCA1), 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 ataxias and 16 individuals
with sporadic cerebellar ataxia were investigated to determine the frequency of
this mutation, the behavior of the SCA1 CAG repeat during transmission, and the
clinical features specific to this form of disease. Only 12 of the families
carried the SCA1 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 SCA1 from other forms of dominantly inherited ataxias. In the
absence of distinguishing clinical characteristics, the diagnosis of SCA1 in
single affected patients or family members can only be made by direct detection
of the mutation, opening the way for presymptomatic testing.
PMID: 7847859 [Indexed for MEDLINE]