Wang Junling, Xu Qian, Lei Lifang, Shen Lu, Jiang Hong, Li Xiaohui, Zhou Yafang, Yi Jiping, Zhou Jie, Yan Xinxiang, Pan Qian, Xia Kun, Tang Beisha
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008 PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009 Dec;26(6):620-5. doi: 10.3760/cma.j.issn.1003-9406.2009.06.004.
To investigate the CAG trinucleotide repeat expansion in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, 12, and 17 from Chinese Han.
The pathological CAG triplet repeat expansions of the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA12 and SCA17 genes were analyzed in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 probands from families with autosomal dominant SCA and 196 sporadic cases. Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technology by T-vector cloning and direct sequencing were performed to detect the CAG-repeat number of abnormal allele.
Among the 559 SCA patients, twenty-three were positive for SCA1, the ranges of expanded CAG repeats were from 39 to 60 (mean:51.09+/-4.88); thirty-two were positive for SCA2, the ranges of expanded CAG repeats were from 36 to 51 (mean:40.34+/-4.40); three hundred and five were positive for SCA3/MJD, the ranges of expanded CAG repeats were from 49 to 86 (mean:73.84+/-5.07); nine were positive for SCA6, the ranges of expanded CAG repeats were from 23 to 29 (mean:25.56+/-1.94); twenty-seven were positive for SCA7, the ranges of expanded CAG repeats were from 38 to 71(mean:58.22+/-10.90); three were positive for SCA12, the ranges of expanded CAG repeats were from 51 to 52 (mean:51.33+/-0.58); and finally, two were positive for SCA17, the range of expanded CAG repeats were from 53 to 55 (mean:54.00+/-1.41).
The 39 CAG repeats of SCA1, 49 CAG repeats of SCA3 and 51 CAG repeats of SCA12 are all the shortest known causative expanded alleles, while the 86 CAG repeats of SCA3/MJD is the largest full expanded allele that has never been reported. Furthermore, it is the first report of SCA17 subtype in Mainland Chinese and first research that established the abnormal reference standard of CAG repeat number of different subtypes of SCA in Chinese Han.
研究中国汉族脊髓小脑共济失调（SCA）1、2、3、6、7、12和17型中的CAG三核苷酸重复扩增情况。
对559例中国大陆脊髓小脑共济失调患者进行分析，检测SCA1、SCA2、SCA3/马查多-约瑟夫病（MJD）、SCA6、SCA7、SCA12和SCA17基因的病理性CAG三联体重复扩增，其中包括363例常染色体显性SCA家系的先证者和196例散发病例。采用聚合酶链反应、琼脂糖凝胶电泳、T载体克隆重组DNA技术及直接测序法检测异常等位基因的CAG重复数。
559例SCA患者中，23例SCA1阳性，CAG重复扩增范围为39至60（平均：51.09±4.88）；32例SCA2阳性，CAG重复扩增范围为36至51（平均：40.34±4.40）；305例SCA3/MJD阳性，CAG重复扩增范围为49至86（平均：73.84±5.07）；9例SCA6阳性，CAG重复扩增范围为23至29（平均：25.56±1.94）；27例SCA7阳性，CAG重复扩增范围为38至71（平均：58.22±10.90）；3例SCA1十二阳性，CAG重复扩增范围为51至52（平均：51.33±0.58）；最后，2例SCA17阳性，CAG重复扩增范围为53至55（平均：54.00±1.41）。
SCA1的39个CAG重复、SCA3的49个CAG重复和SCA12的51个CAG重复均为已知最短的致病性扩增等位基因，而SCA3/MJD的86个CAG重复是从未报道过的最大的完全扩增等位基因。此外，这是中国大陆SCA17亚型的首次报道，也是首次建立中国汉族SCA不同亚型CAG重复数异常参考标准的研究。
