脊髓小脑共济失调3型家系CAG动态突变分析和产前诊断

Dynamic mutation analysis of a SCA3 Chinese Han family and prenatal diagnosis

目的探讨脊髓小脑共济失调3型患者的临床特点、分子遗传学特征及产前诊断的意义。方法采用聚合酶链反应及DNA片段分析技术对脊髓小脑共济失调3型一家系4代共9例患者(其中1例为先证者之4月龄胎儿)中的2例患者施行SCA3/ATXN3基因(CAG)n重复数目分析。结果一家系中4代共9例患者发病均符合常染色体显性遗传特征,其中8例患者(除外先证者之4月龄胎儿)均以步态不稳为首发症状,伴发不同程度构音障碍;先证者神经系统检查显示共济失调伴眼球上视受限及锥体束损害体征。其中第1代患者于50岁左右发病、第2代患者40～45岁发病、第3代(先证者)28岁发病,发病年龄呈逐代提前现象。先证者SCA3/ATXN3基因(CAG)n重复数目为77次(>44次),其4月龄胎儿(CAG)n重复数目也为77次,通过产前诊断证实亦为脊髓小脑共济失调3型患者。结论脊髓小脑共济失调3型是亚洲人种中最常见的脊髓小脑共济失调亚型,以步态不稳为首发症状,除小脑性共济失调外尚可伴发其他临床表现。家系中存在遗传早现现象,但其CAG动态突变率较小。脊髓小脑共济失调3型病因明确但无有效治疗方法,对患者进行遗传咨询并对其胎儿进行产前诊断,是预防和中断遗传链之关键措施。

Objective To explore the clinical features, genetic characters and the importance of prenatal diagnosis in spinocerebellar ataxia 3 （SCA3） patients. Methods SCA3/ATXN3 gene was determined by using PCR and segmental analysis techniques in 2 patients among a SCA3 Chinese Han family which included 9 patients in four generations. One patient was the proband＇s fetus. The clinical characters were also documented and analyzed in this family. Results There were 9 patients in this family with autosomal dominant inheritance feature. The initial symptoms in all affected members except the fetus were the gait disorders accompanied by dysphasia. Inability of upward gaze and bilateral Barbinski＇s signs were noted in proband. The onset age became earlier from generation to generation in this family which was around 50 year-old, 40 to 45 year-old, 28 year-old in generation I, II and VI, respectively. CAG repeats in SCA3/ATXN3 allele were 77 in proband, as well as in the fetus, while the normal SCA3/ATXN3 allele CAG repeats were less than 44. Conclusion SCA3 is the most frequent subtype of SCA in Asian. Unsteadiness of gait are first noted in most patients accompanied by other different symptoms and signs. Genetic anticipation was found in SCA3. But gene analysis revealed less dynamic mutation frequence in this family. Since there was no effective treatment in SCA3, hereditary consultation and prenatal diagnosis play an important role in disease prevention and hereditary.