Participation of new CAG repeat gene in Spinocerebellar ataxia.

我们筛选脊髓小脑性共济失调14型（SCA14）和脊髓小脑性共济失调16型（SCA16）。据报道，SCA14的致病基因是PRKCG基因（编码蛋白激酶C γ亚型），SCA16的致病基因是Contaxin4 （CNTN4）基因。我们在882例病因不明的SCA患者中筛选了PRKCG基因的外显子4。我们在一个家族中发现了一种新的C/T错义突变，具有ser119到Phe替代（S119F）。主要症状为单纯小脑性共济失调，发病晚。1例患者表现为顽固性癫痫，严重行走障碍，躯干共济失调早发。提示日本SCA人群中SCA14的频率很低。接下来，我们检测了323例SCA患者CNTN4基因的c.4256C>T突变。我们没有发现突变，似乎这种突变在日本遗传性脊髓小脑性共济失调患者中很少见。这种c.4256C>T的替换可能是第一个报道的家族所特有的，而不是一般的致病基因。在我们的遗传性SCA样本中，SCA6占25.3%，并且是最常见的。其次MJD/SCA3为23.1%，DRPLA为8.2%，SCA1为4.0%，未知致病基因为34.8%。我们对来自欧洲、南美和远东地区的SCA6家族进行了单倍型分析。在全球受影响的个体中发现了核心CACNA1A疾病单倍型。这也出现在新发病例的未受影响的父亲身上，表明共享染色体易导致SCA6位点的CAG重复扩增。我们筛选了CAG扩增的候选基因，存在异质性。其模式与正常对照相似，没有扩增CAG重复序列的基因。

We screened spinocerebellar ataxia type 14 (SCA14) and spinocerebellar ataxia type 16 (SCA16). It is reported that the causative gene of SCA14 is PRKCG gene (encoding γ subtype of protein kinase C) and SCA16 is Contaxin4 (CNTN4) gene. We screened exon4 of the PRKCG gene in 882 SCA patients with undefined etiologies. We found a novel C/T missense mutation with a Ser119-to Phe substitution (S119F) in one family. The main symptom was pure cerebellar ataxia with late onset. One patient showed intractable epilepsy, severe walking disturbance, and trunk ataxia with early onset. It is suggested that the frequency of SCA14 in the Japanese SCA population is very low. Next, we examined c.4256C>T mutation of CNTN4 gene in 323 SCA patients. We found no mutation, and it seemed that this mutation is rare in Japanese with inherited spinocerebellar ataxia. This c.4256C>T substitution may be specific to the first reported family, and not a causative gene in general In our inherited SCA samples, SCA6 is 25.3% and most frequent. Next MJD/SCA3 is 23.1%, DRPLA is 8.2%, SCA1 is 4.0%, and unknown causative gene is 34.8%.We carried out haplotype analysis on SCA6 families from Europe, South America and the Far East. A core CACNA1A disease haplotype was found in affected individuals across the globe. This was also present in the unaffected father of the de novo case, suggesting that the shared chromosome predisposes to the CAG repeat expansion at the SCA6 locus.We screened the candidate genes that have CAG expansions, and heterogeneity were existed. Its pattern is similar to normal control, and there was no gene that have expanded CAG repeats.