Wang Junling, Shen Lu, Lei Lifang, Xu Qian, Zhou Jie, Liu Yutao, Guan Wenjuan, Pan Qian, Xia Kun, Tang Beisha, Jiang Hong
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Jun;36(6):482-9. doi: 10.3969/j.issn.1672-7347.2011.06.003.
To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China.
SCA 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) nucleotide repeat mutations were detected in 430 families with autosomal dominant SCA (ADCA) and 237 patients with sporadic ataxias by PCR and DNA sequencing. Subsequently, point and Indel (Insertion/deletion) mutation analyses of SCA5, SCA11, SCA13, SCA14, SCA15/16/29, SCA27, SCA31 and SCA35 were detected in 91 families with ADCA and 196 patients with sporadic ataxias excluded from SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA genotypes via PCR and Denaturing High Performance Liquid Chromatography (PCR-DHPLC), Multiplex ligation-dependent probe amplification and DNA direct sequencing analysis.
Among the 430 ADCA families, there were 25 SCA1 (5.81%), 27 SCA2 (6.28%), 267 SCA3/MJD (62.09%), 8 SCA6 (1.86%), 8 SCA7 (1.86%), 1 SCA12 (0.23%), 1 SCA17 (0.23%) and 2 SCA35 (0.47%), and the remaining 91 families (21.16%) were genetically unidentified. Among the 237 sporadic SCA patients, there were 6 SCA1 (2.53%), 9 SCA2 (3.80%), 23 SCA3/MJD (9.70%) and 3 SCA6 (1.27%), and the remaining 196 (82.7%) were genetically unidentified. No pathogenic point mutation causing SCA5, SCA11, SCA13, SCA14, SCA27 or SCA31 subtypes was found.
SCA3/MJD is substantially the most common subtype in patients with ADCA and sporadic forms in mainland China, followed by SCA2, SCA1, SCA6 and SCA7. While SCA12, SCA17 and SCA35 are seldom found, SCA5, SCA8, SCA10, SCA11, SCA13, SCA27, SCA31 and DRPLA are very rare. The high proportion of genetically unidentified cases further verify that SCAs are of highly genetic heterogeneity, suggesting that other disease-causing genes might be involved in the negative ADCA pedigrees, and other etiological factors may involve in those sporadic cases other than genetics.
对中国大陆遗传性脊髓小脑共济失调（SCA）患者进行最新的基因谱分析。
采用聚合酶链反应（PCR）和DNA测序技术，对430个常染色体显性遗传性脊髓小脑共济失调（ADCA）家系及237例散发性共济失调患者进行SCA 1、2、3、6、7、8、10、12、17型及齿状核红核苍白球路易体萎缩症（DRPLA）核苷酸重复突变检测。随后，采用PCR及变性高效液相色谱法（PCR-DHPLC）、多重连接依赖探针扩增技术及DNA直接测序分析，对91个ADCA家系及196例排除SCA1、2、3、6、7、8、10、12、17型及DRPLA基因型的散发性共济失调患者进行SCA5、SCA11、SCA13、SCA14、SCA15/16/29、SCA27、SCA31及SCA35型的点突变和插入/缺失（Indel）突变分析。
在430个ADCA家系中，SCA1型25个（5.81%），SCA2型27个（6.28%），SCA3/MJD型267个（62.09%），SCA6型8个（1.86%），SCA7型8个（1.86%），SCA12型1个（0.23%），SCA17型1个（0.23%），SCA35型2个（0.47%），其余91个家系（21.16%）基因类型未明确。在237例散发性SCA患者中，SCA1型6个（2.53%），SCA2型9个（3.80%），SCA3/MJD型23个（9.70%），SCA6型3个（1.27%），其余196个（82.7%）基因类型未明确。未发现导致SCA5、SCA11、SCA13、SCA14、SCA27或SCA31亚型的致病性点突变。
在中国内地，SCA3/MJD是ADCA患者及散发性患者中最常见的亚型，其次是SCA2、SCA1、SCA6和SCA7。SCA12、SCA17和SCA35很少见，SCA5、SCA8、SCA10、SCA11、SCA13、SCA27、SCA31和DRPLA非常罕见。基因类型未明确病例的高比例进一步证实SCA具有高度的遗传异质性，提示在ADCA阴性家系中可能涉及其他致病基因，而在散发性病例中除遗传因素外可能还涉及其他病因。
