Multiple origins of the spinocerebellar ataxia 7 (SCA7) mutation revealed by linkage disequilibrium studies with closely flanking markers, including an intragenic polymorphism (G3145TG/A3145TG).
Eur J Hum Genet. 1999-12-01; 7(8): 889-896
DOI: 10.1038/sj.ejhg.5200392
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1. Eur J Hum Genet. 1999 Dec;7(8):889-96.
Multiple origins of the spinocerebellar ataxia 7 (SCA7) mutation revealed by
linkage disequilibrium studies with closely flanking markers, including an
intragenic polymorphism (G3145TG/A3145TG).
Stevanin G(1), David G, Dürr A, Giunti P, Benomar A, Abada-Bendib M, Lee MS, Agid
Y, Brice A.
Author information:
(1)INSERM U289, Hôpital de la Salpêtrière.
Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease characterised by
the association of cerebellar ataxia and, in most patients, progressive macular
degeneration leading to loss of autonomy and blindness. The patients die after
5-30 years of evolution. The cause of the disease has been identified as a (CAG)n
repeat expansion in the coding sequence of the SCA7 gene on chromosome 3p. De
novo mutations occur on intermediate-sized alleles carrying from 28 to 35 CAG
repeats. Neomutations explain the persistence of the disease in spite of the
great instability of the repeat sequence which results in the appearance of
juvenile onset patients and the extinction of the disease within families. This
rare disorder has been reported in a wide variety of countries and ethnic groups.
In a large number of SCA7 families (n = 41) of different origins, we have
determined the haplotypes segregating with the mutation of several microsatellite
markers close to the SCA7 gene and of a new intragenic polymorphism
(G3145TG/A3145TG). Four different haplotypes were found for centromeric markers
(G3145TG/A3145TG-D3S1287-D3S3635) in the majority of the kindreds from four
different geographic regions: A-2-4 in Korea; A-3-6 in North Africa, B-3-6 in
continental Europe and A-4-6 in the UK and USA. The haplotypes in the Jamaican,
Filipino, Brazilian and German families were different, suggesting that
independent regional founders are at the origin of the SCA7 mutation in each
population. Two different haplotypes were observed, however, in two families from
the same rural area in central Italy in which de novo SCA7 mutations on
intermediate alleles have been observed, suggesting the existence of different
pools of at-risk chromosomes in this population.
DOI: 10.1038/sj.ejhg.5200392
PMID: 10602364 [Indexed for MEDLINE]