Didierjean O, Cancel G, Stevanin G, Dürr A, Bürk K, Benomar A, Lezin A, Belal S, Abada-Bendid M, Klockgether T, Brice A
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
J Med Genet. 1999 May;36(5):415-7.
Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.
2型脊髓小脑共济失调（SCA2）由编码多聚谷氨酰胺序列的不稳定CAG重复序列扩增所致。含有32至200个CAG的重复序列与该疾病相关，而正常染色体含有13至33个重复序列。我们对220个不同地理来源的家族进行了SCA2突变检测。33个家族呈阳性（15%）。对23个至少有两名受累个体的家族进行了SCA2突变与三个微卫星标记之间的连锁不平衡（LD）检测，其中两个标记（D12S1332 - D12S1333）紧密侧翼于该突变；另一个（D12S1672）位于基因内。观察到许多不同的单倍型，表明发生了几种祖先突变。然而，在德国、塞尔维亚和一些法国家族中检测到了一种在对照中未观察到的相同单倍型，提示存在奠基者效应或在风险单倍型上的反复突变。
