Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families
Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families
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DOI：
10.1007/s10038-007-0182-x
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发表时间：
2007-10-01
影响因子：
3.5
通讯作者：
Sasaki, Hidenao
中科院分区：
文献类型：
--
作者：
Basri, Rehana;Yabe, Ichiro;Sasaki, Hidenao
常染色体显性遗传性小脑共济失调（ADCA）是一组遗传异质性的神经退行性疾病。为了进一步阐明日本ADCA的临床和遗传谱，我们进行了一项研究，以确定ADCA患者中各种新的不同SCA亚型的频率。本研究于1999年4月至2006年12月在具有ADCA疾病症状和体征的患者中进行。共对113个家系进行了PCR和/或直接测序。其中SCA 6突变35个，SCA 3突变30个，SCA 1突变11个，SCA 2突变5个，DRPLA突变5个，SCA 14突变1个。我们还在10个家系中检测到puratrophin-1基因内杂合的-16C -> T单核苷酸取代，导致16q22.1连锁的ADCA。本研究未发现27、13、5、7、8、12、17和16例SCA异常变异，113例患者中14%存在尚未鉴定的ADCA突变。本研究验证了基于种族起源和地理变异的遗传学上不同的ADCA亚型的患病率，并表明16 q连锁的ADCA在日本ADCA患者中具有强烈的遗传效应。
Autosomal dominant cerebellar ataxia (ADCA) is a genetically heterogeneous group of neurodegenerative disorders. To shed further light on the clinical and genetic spectrum of ADCA in Japan, we conducted a study to determine the frequency of a new variety of different subtypes of SCAs among ADCA patients. This current study was carried out from April 1999 to December 2006 on the basis of patients with symptoms and signs of ADCA disorders. PCR and/or direct sequencing were evaluated in a total of 113 families. Among them, 35 families were found to have the mutation associated with SCA6, 30 with SCA3, 11 with SCA1, five with SCA2, five with DRPLA, and one with SCA14. We also detected the heterozygous -16C -> T single nucleotide substitution within the puratrophin-1 gene responsible for 16q22.1-linked ADCA in ten families. In this study, unusual varieties of SCA, including 27, 13, 5, 7, 8, 12, 17, and 16 were not found. Of the 113 patients, 14% had as yet unidentified ADCA mutations. The present study validates the prevalence of genetically distinct ADCA subtypes based on ethnic origin and geographical variation, and shows that 16q-linked ADCA has strong hereditary effects in patients with ADCAs in Japan.