权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Participation of new CAG repeat gene in Spinocerebellar ataxia.

新CAG重复基因参与脊髓小脑共济失调。

基本信息

批准号：
18590943
负责人：
MARUYAMA Hirofumi
金额：
$ 2.45万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590943/
关键词：
CAG repeat expansion Spinocerebellar ataxia

项目摘要

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.

我们筛选了脊髓小脑共济失调14型（SCA 14）和脊髓小脑共济失调16型（SCA 16）。SCA 14的致病基因为PRKCG基因（编码γ亚型蛋白激酶C），SCA 16为Contaxin 4（CNTN 4）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。我们在一个家系中发现了一个新的C/T错义突变，即Ser 119-替换为Phe（S119 F）。主要症状为迟发性单纯小脑性共济失调。1例患者表现为顽固性癫痫、严重行走障碍和躯干共济失调，早期发作。这表明日本SCA群体中SCA 14的频率很低。接下来，我们检测了323例SCA患者的CNTN 4基因c.4256C>T突变。我们没有发现突变，似乎这种突变是罕见的日本遗传性脊髓小脑共济失调。这种c.4256C>T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，SCA 6是25.3%和最常见的。其次是MJD/SCA 3占23.1%，DRPLA占8.2%，SCA 1占4.0%，未知致病基因占34.8%。在地球仪的受影响个体中发现了核心CACNA 1A疾病单倍型。这也存在于新发病例的未受影响的父亲中，表明共享染色体易于在SCA 6位点进行CAG重复扩增。其模式与正常对照相似，没有CAG重复序列扩增的基因。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A polymorphism of LOC387715 gene is associated with age-related macular degeneration in the Japanese population

LOC387715基因多态性与日本人群年龄相关性黄斑变性有关

DOI：
发表时间：
2007
期刊：
Neuroscience Letters 414
影响因子：
0
作者：
S Tanimoto;H Maruyama;H Kawakami;et. al.
通讯作者：
et. al.

Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome?

SCA6 基因座的致病性扩展与全球常见的 CACNA1A 单倍型相关：创始人效应还是易感染色体？

DOI：
发表时间：
2008
期刊：
European Journal of Human Genetics Epub(印刷中)
影响因子：
0
作者：
K Craig;H Maruyama;H Kawakami;et. al.
通讯作者：
et. al.

The CNTN4 c. 4256C>T mutation is rare in Japanese with inherited spinocerebellar ataxia.

CNTN4 c．

DOI：
发表时间：
2008
期刊：
J Neurol Sci 266(1-2)
影响因子：
0
作者：
Tanaka E;Maruyama H;Morino H;Nakajima E;Kawakami H
通讯作者：
Kawakami H

Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe : founder effect or predisposing chromosome?

SCA6 基因座的致病性扩展与全球常见的 CACNA1A 单倍型相关：创始人效应还是易感染色体？

DOI：
发表时间：
期刊：
European Journal of the Human Genetics (in press)
影响因子：
0
作者：
K.;Craig;Y.;Takiyama;B-W.;Soong;LB.;Jaardim;ML.;Saraiva-Pereira;K.;Lythgow;H.;Morino;H.;Maruyama;H.;Kawakami;PF.;Chinnery
通讯作者：
Chinnery

Identification of a new family of spinocerebellar ataxia type 14 in the Japanese spinocerebellar ataxia population by the screening of PRKCG exon 4