Participation of new CAG repeat gene in Spinocerebellar ataxia.

我们筛查了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的致病基因是编码蛋白激酶C的γ亚型的PRKCG基因，而SCA16的致病基因是趋化蛋白4(CNTN4)基因。我们对882例病因不明的SCA患者进行了PRKCG基因外显子4的筛查。我们在一个家系中发现了一个新的C/T错义突变，该突变带有Ser119-to Phe替换(S119F)。主要症状为单纯小脑性共济失调，起病晚。1例表现为顽固性癫痫、严重行走障碍和躯干共济失调，起病早。提示SCA14基因在日本SCA人群中的频率很低。接下来，我们对323例SCA患者进行了CNTN4基因c.4256C&GT；T突变的检测。我们没有发现突变，而且这种突变似乎在患有遗传性脊髓小脑性共济失调的日本人中是罕见的。这种c.4256C&gt；T替换可能是第一个报道的家系所特有的，在我们的遗传性SCA样本中，SCA6是25.3%，是最常见的致病基因。其次是MJD/SCA3占23.1%，DRPLA占8.2%，SCA1占4.0%，未知致病基因占34.8%。在全球受影响的个体中发现了核心CACNA1A病单倍型。这一点也存在于新发病例的父亲中，这表明共享的染色体易于在SCA6基因座发生CAG重复扩增。我们筛选了具有CAG扩增的候选基因，并且存在异质性。其模式与正常对照相似，并且没有扩增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.