广东汉族人遗传性脊髓小脑型共济失调基因突变的研究

目的 研究广东汉族人遗传性脊髓小脑型共济失调（SCA）的亚型（SCA1、SCA2、SCA3和SCA7）基因突变分布频率。方法 对临床诊断为SCA的18个家系24例SCA患者、22例散发SCA患者、45名家系“正常人”及30名非家系健康人,通过聚合酶链反应（PCR）及聚丙烯酰胺凝胶电泳（PAGE）等技术检测SCA1、2、3、7基因内CAG三核苷酸重复序列突变,并利用ABI310、377测序仪对异常等位基因片段进行DNA测序。结果 在18个SCA家系中,1个家系（5.55％）有SCA1基因突变,2个家系（11.11％）有SCA2基因突变,7个家系（38.88％）有SCA3基因突变,未发现SCA7突变,。在家系成员中检出1例症状前SCA3患者。22例散发性患者中检出SCA1、SCA2、SCA3和SCA7各1例,各占4.54％。SCA1患者CAG重复数为53～56次,正常人19～34次;SCA2患者CAG重复数为38～45次,正常人20～25次;SCA3患者CAG重复数为74～81次,正常人14～40次。SCA7患者CAG重复数为65次,正常人为9～19次。结论 提示中国人SCA主要为SCA3/MJD型,其次为SCA2和SCA1。基因分析对家族性以及散发性SCA患者的临床确诊和遗传咨询均有重要意义。

A research on trinucleotide dynanic mutation of hereditary spinocerebellar ataxia in Cantonese with Han nationality

Objective To study frequency and clinical characteristics of the mutation SCA1, SCA2, SCA3 and SCA7 among Cantonese(Han nationality) SCA patients. Methods The SCAl, 2, 3, 7 (CAG)n mutations were detected by polymerase chain reaction (PCR) , denaturing polyacrylamide gel electrophoresis and silver staining technique in 24 patients with autosomal dominant SCA from 18 families and in 22 sporadic SCA patients. The abnormal allele fragments were sequeneed by AB1310 or 377 DNA sequencing machine. Results Among 18 kindreds, 5.55%(l/18) were positive for SCAl; 11.11%(2/18) were positive for SCA2; 38.88%(7/18) were positive for SCA3; none was positive for SCA7. One presymtomatic SCA3 patient was detected in family members. Among 22 sporadic SCA patients, one (4.54% ) was positive for every subtype we examined. In SCA1 patients, the CAG repeat was expanded to 53 ~ 56 repeats, whereas in normal individuals if was 19 - 34 repeats. In SCA2 patients the GAG repeat was expanded to 38 ~ 45 repeats, whereas in normal individuals it was 20 ~ 25 repeats. In SCA3 patients the CAG repeat was expanded to 74 ~ 81 repeats, whereas in normal individuals it was 14 ~ 40 repeats. In SCA7 patient, the CAG repeat was expanded to 65 repeats, whereas in normal ones it was 9 ~ 19 repeats. Conclusions The frequency of SCA3/MJD is substantially higher than that of SCAl and SCA2 in the autosomal dominant SCA from Chinese families. It is of great significance for definite diagnosis and genetic counseling to carry gene analysis in both familial and sporadic SCA patients.