Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families.
Human Molecular Genetics. 1997-05-01; 6(5): 709-715
DOI: 10.1093/hmg/6.5.709
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1. Hum Mol Genet. 1997 May;6(5):709-15.
Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32
families.
Cancel G(1), Dürr A, Didierjean O, Imbert G, Bürk K, Lezin A, Belal S, Benomar A,
Abada-Bendib M, Vial C, Guimarães J, Chneiweiss H, Stevanin G, Yvert G, Abbas N,
Saudou F, Lebre AS, Yahyaoui M, Hentati F, Vernant JC, Klockgether T, Mandel JL,
Agid Y, Brice A.
Author information:
(1)INSERM U289, Paris, France.
Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG
repeat encoding a polyglutamine tract. One hundred and eighty four index patients
with autosomal dominant cerebellar ataxia type I were screened for this mutation.
We found expansion in 109 patients from 30 families of different geographical
origins (15%) and in two isolated cases with no known family histories (2%). The
SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch
of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14
repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by
unstable mutations, a strong negative correlation was observed between the age at
onset and the size of the CAG repeat (r = -0.81). The frequency of several
clinical signs such as myoclonus, dystonia and myokymia increased with the number
of CAG repeats whereas the frequency of others was related to disease duration.
The CAG repeat was highly unstable during transmission with variations ranging
from -8 to +12, and a mean increase of +2.2, but there was no significant
difference according to the parental sex. This instability was confirmed by the
high degree of gonadal mosaicism observed in sperm DNA of one patient.
DOI: 10.1093/hmg/6.5.709
PMID: 9158145 [Indexed for MEDLINE]