Identification of a new family of spinocerebellar ataxia type 14 in the Japanese spinocerebellar ataxia population by the screening of PRKCG exon 4
Identification of a new family of spinocerebellar ataxia type 14 in the Japanese spinocerebellar ataxia population by the screening of PRKCG exon 4
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DOI：
10.1002/mds.20970
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发表时间：
2006-09-01
影响因子：
8.6
通讯作者：
Sakai, Norio
中科院分区：
文献类型：
--
作者：
Hiramoto, Keiko;Kawakami, Hideshi;Sakai, Norio
脊髓小脑性共济失调14型（SCA14）是一种常染色体显性神经退行性疾病，以小脑性共济失调和间歇性轴性肌阵挛为特征。在SCA14家族中发现了编码蛋白激酶C γ的PRKCG基因的各种突变。这些突变大多发生在PRKCG基因的外显子4上。我们进行了基于聚合酶链反应（PCR）的筛选，以澄清日本SCA人群中该疾病的大致发病率。我们在882例病因不明的SCA患者中筛选了PRKCG基因外显子4，使用变性高效液相色谱和随后的直接测序。我们在2例患者中发现了一种新的C/T错义突变，具有Ser119-to-Phe替代（S119F），随后发现他们属于同一家族。在259个对照个体中未发现S119F突变。进一步基于pcr的分析显示，该家族中还有另外5名成员具有相同的突变。其中5例表现为小脑性共济失调。5例患者中4例以单纯小脑性共济失调为主，发病晚。他们没有肌阵挛、锥体外系症状、眼麻痹或智力障碍，其中一些在先前报道的SCA家族中发现。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。本研究结果表明，日本SCA人群中SCA14的频率非常低。(c) 2006年运动障碍协会。
Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia and intermittent axial myoclonus. Various mutations have been found in the PRKCG gene encoding protein kinase C gamma in SCA14 families. Most of those mutations have been found in exon 4 of the PRKCG gene. We performed polymerase chain reaction (PCR)-based screening to clarify the approximate morbidity rate of the disease in the Japanese SCA population. We screened exon 4 of the PRKCG gene in 882 SCA patients with undefined etiologies using denaturing high-performance liquid chromatography and subsequent direct sequencing. We found a novel C/T missense mutation with a Ser119-to-Phe substitution (S119F) in 2 patients and subsequently found that they belonged to the same family. This S119F mutation was not found in 259 control individuals. Further PCR-based analysis revealed an additional 5 members with the same mutation in this family. Cerebellar ataxia was manifested in 5 of those 7 members. The main symptom in 4 of the 5 affected members was pure cerebellar ataxia with late onset. They had no myoclonus, extrapyramidal signs, ophthalmoplegia, or intellectual disturbance, some of which were found in previously reported SCA families. One patient showed intractable epilepsy, severe walking disturbance, and trunk ataxia with early onset. The results of this study suggest that the frequency of SCA14 in the Japanese SCA population is very low. (c) 2006 Movement Disorder Society.