Cancel G, Abbas N, Stevanin G, Dürr A, Chneiweiss H, Néri C, Duyckaerts C, Penet C, Cann H M, Agid Y
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Am J Hum Genet. 1995 Oct;57(4):809-16.
The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with those with Machado-Joseph disease (MJD), the gene of which maps to the same region. We show here that the disease gene segregating in each of three French ADCA type I kindreds and in a French family with neuropathological findings suggesting the ataxochoreic form of dentatorubropallidoluysian atrophy carries an expanded CAG repeat sequence located at the same locus as that for MJD. Analysis of the mutation in these families shows a strong negative correlation between size of the expanded CAG repeat and age at onset of clinical disease. Instability of the expanded triplet repeat was not found to be affected by sex of the parent transmitting the mutation. Evidence was found for somatic and gonadal mosaicism for alleles carrying expanded trinucleotide repeats.
I型常染色体显性小脑共济失调（ADCA I型）是一组临床和遗传异质性的神经退行性疾病，其脊髓小脑共济失调3型（SCA3）基因座已被定位于染色体14q32.1。来自分离SCA3的家族的ADCA I型患者与马查多-约瑟夫病（MJD）患者具有共同的临床特征，后者的基因也定位于同一区域。我们在此表明，在三个法国ADCA I型家族以及一个有神经病理学发现提示为齿状核红核苍白球路易体萎缩的共济失调舞蹈病型的法国家族中，各自分离的疾病基因都携带一个位于与MJD相同基因座的CAG重复序列的扩增。对这些家族中突变的分析表明，扩增的CAG重复序列的大小与临床疾病发病年龄之间存在很强的负相关。未发现扩增的三联体重复序列的不稳定性受传递突变的亲本性别影响。发现了携带扩增三核苷酸重复序列的等位基因存在体细胞和生殖腺嵌合现象的证据。
