Prevalence of spinocerebellar ataxia type 2 mutation among Italian parkinsonian patients
Prevalence of spinocerebellar ataxia type 2 mutation among Italian parkinsonian patients
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DOI：
10.1002/mds.21228
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发表时间：
2007-02-15
影响因子：
8.6
通讯作者：
Silvestri, Gabriella
中科院分区：
文献类型：
--
作者：
Modoni, Anna;Contarino, Maria Fiorella;Silvestri, Gabriella
我们评估了224名患有典型帕金森症的意大利患者中SCA2基因突变的发生率，其中包括145种散发形式和79种家族性形式。PINK1、Parkin和LRRK2基因突变此前已被排除。对白细胞DNA进行SCA2位点CAG扩增的分子检测。对SCA2扩增阳性的患者进行扩增等位基因的克隆和测序。在研究的79个家系中，有1个家系检测到38个CAG扩增。先证者是一名67岁的男性，他和他69岁的妹妹都受到了一种良性形式的L-多巴反应性帕金森症的影响，与小脑体征无关。该遗传为常染色体显性遗传。通过减数分裂传递，CAG伸展稳定：序列分析表明，CAG伸展被3个CAA打断。我们的研究表明，在意大利患者中，SCA2基因的CAG扩增可能代表了家族性L多巴反应性帕金森综合征的遗传原因。在该家系中检测到的病理性CAG扩张的稳定性与CAA中断的存在有关。这些发现与文献数据一起表明，扩展等位基因的分子内在结构可能调节SCA2突变的表型表达。(C)2006年运动无序协会。
We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L-dopa-responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L-dopa-responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation. (C) 2006 Movement Disorder Society.