CAJ | 학술논문

中国大陆脊髓小脑性共济失调家系和散发病例的最新基因突变分析
중국대륙척수소뇌성공제실조가계화산발병례적최신기인돌변분석
Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases

万方数据

中南大学学报（医学版）中南大學學報（醫學版） 중남대학학보（의학판）
JOURNAL OF CENTRAL SOUTH UNIVERSITY (MEDICAL SCIENCES)
2011年 6期 482-489 ,共8页

王俊岭%沈璐%雷立芳%徐倩%周洁%刘玉涛%关文娟%潘乾%夏昆%唐北沙%江泓

왕준령%침로%뢰립방%서천%주길%류옥도%관문연%반건%하곤%당북사%강홍

脊髓小脑性共济失调%核苷酸重复%点突变%基因突变分析脊髓小腦性共濟失調%覈苷痠重複%點突變%基因突變分析
척수소뇌성공제실조%핵감산중복%점돌변%기인돌변분석
spinocerebellar ataxia%nucleotide repeat%point mutation%genetic analysis

目的:了解中国大陆汉族人群常染色体显性遗传和散发脊髓小脑性共济失调(SCA)中最新基因频率分布.方法:采用聚合酶链反应(PCR)和DNA直接测序(DNA sequencing)方法对430例常染色体显性遗传SCA(AD-SCA)家系先证者和237例散发患者进行了SCA1,SCA2,SCA3/MJD,SCA6,SCA7,SCA8,SCA10,SCA12,SCA17亚型和齿状核红核苍白球路易体萎缩(DRPLA)亚型致病基因核苷酸重复突变检测分析,然后采用聚合酶链反应-变性高效液相色谱(PCR-DHPLC),多重连接探针扩增(MLPA)和DNA直接测序方法对91例排除了以上SCA亚型突变的ADCA家系先证者和196例散发患者进行了SCA5,SCA11,SCA13,SCA14,SCA15/16/29,SCA27,SCA31和SCA35亚型的点突变及插入缺失突变检测.结果:在430个AD-SCA家系中,发现有25个SCA1家系(5.81%)、27个SCA2家系(5.81%)、267个SCA3/MJD家系(62.09%)、8个SCA6家系(1.86%)、8个SCA7家系(1.86%)、1个SCA12家系(0.23%)、1个SCA17家系(0.23%)和2个SCA35家系(0.47%),91个ADCA家系未明确基因分型(21.16%);在237例散发SCA患者中,发现有6例SCA1患者(2.53%)、9例SCA2患者(3.80%)、23例SCA3/MJD患者(9.70%)和3例SCA6患者(1.27%),196例SCA患者未明确基因分型(82.7%);未发现SCA8,SCA10和DRPLA亚型核苷酸重复突变和SCA5,SCA11,SCA13,SCA14,SCA15/16/29,SCA27和 SCA31亚型点突变或插入缺失突变.结论:在中国汉族人群中SCA3/MJD为最常见的SCA亚型,其次为SCA2,SCA1,SCA6和SCA7亚型,SCA12,SCA17和SCA35亚型比较少见,SCA5,SCA8,SCA10,SCA11,SCA13,SCA14,SCA15/16/29,SCA27,SCA31和DRPLA亚型罕见.在ADCA家系和散发患者中存在一定比例基因型暂不明的病例,说明SCA的遗传异质性,可能是由于部分ADCA家系存在其他致病基因的作用,大部分散发SCA患者除遗传因素外还存在其他致病因素.
목적:료해중국대륙한족인군상염색체현성유전화산발척수소뇌성공제실조(SCA)중최신기인빈솔분포.방법:채용취합매련반응(PCR)화DNA직접측서(DNA sequencing)방법대430례상염색체현성유전SCA(AD-SCA)가계선증자화237례산발환자진행료SCA1,SCA2,SCA3/MJD,SCA6,SCA7,SCA8,SCA10,SCA12,SCA17아형화치상핵홍핵창백구로역체위축(DRPLA)아형치병기인핵감산중복돌변검측분석,연후채용취합매련반응-변성고효액상색보(PCR-DHPLC),다중련접탐침확증(MLPA)화DNA직접측서방법대91례배제료이상SCA아형돌변적ADCA가계선증자화196례산발환자진행료SCA5,SCA11,SCA13,SCA14,SCA15/16/29,SCA27,SCA31화SCA35아형적점돌변급삽입결실돌변검측.결과:재430개AD-SCA가계중,발현유25개SCA1가계(5.81%)、27개SCA2가계(5.81%)、267개SCA3/MJD가계(62.09%)、8개SCA6가계(1.86%)、8개SCA7가계(1.86%)、1개SCA12가계(0.23%)、1개SCA17가계(0.23%)화2개SCA35가계(0.47%),91개ADCA가계미명학기인분형(21.16%);재237례산발SCA환자중,발현유6례SCA1환자(2.53%)、9례SCA2환자(3.80%)、23례SCA3/MJD환자(9.70%)화3례SCA6환자(1.27%),196례SCA환자미명학기인분형(82.7%);미발현SCA8,SCA10화DRPLA아형핵감산중복돌변화SCA5,SCA11,SCA13,SCA14,SCA15/16/29,SCA27화 SCA31아형점돌변혹삽입결실돌변.결론:재중국한족인군중SCA3/MJD위최상견적SCA아형,기차위SCA2,SCA1,SCA6화SCA7아형,SCA12,SCA17화SCA35아형비교소견,SCA5,SCA8,SCA10,SCA11,SCA13,SCA14,SCA15/16/29,SCA27,SCA31화DRPLA아형한견.재ADCA가계화산발환자중존재일정비례기인형잠불명적병례,설명SCA적유전이질성,가능시유우부분ADCA가계존재기타치병기인적작용,대부분산발SCA환자제유전인소외환존재기타치병인소.
Objective To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China. Methods 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. Results 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. Conclusion 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.