摘要： 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。
关键词:
脊髓小脑共济失调,
三核苷酸重复扩增,
遗传咨询,
产前诊断
Abstract: 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 Ⅲ, 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.
Key words:
Spinocerebellar ataxias,
Trinucleotide repeat expansion,
Genetic counseling consultation,
Prenatal diagnosis
利婧，张成，詹益鑫，冯善伟，杨娟，操基清，喻长顺，李亚勤，王艳云，陈菲，孔杰，郑民缨，廖玲. 脊髓小脑共济失调3型家系CAG 动态突变分析和产前诊断[J]. 中国现代神经疾病杂志, 2012, 12(3): 282-287.
LI Jing, ZHANG Cheng, ZHAN Yi-xin, FENG Shan-wei, YANG Juan, CAO Ji-qing, YU Chang-shun, LI Ya-qin, WANG Yan-yun, CHEN Fei, KONG Jie, ZHENG Min-ying, LIAO Ling. Dynamic mutation analysis of a SCA3 Chinese Han family and prenatal diagnosis[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2012, 12(3): 282-287.