常染色体隐性遗传早发性帕金森综合征6型PINK1基因的突变分析

目的探讨常染色体隐性遗传早发性帕金森综合征6型(PARK6)。PINK1基因的突变及临床特征。方法应用聚合酶链反应(PCR)、DNA直接测序和限制性内切酶酶切等技术对11个常染色体隐性遗传早发性帕金森综合征家系先证者进行PINKl基因的突变分析。结果在两个家系中检测出PINK1基因两个新的点突变：位于第4外显子938位的C→T,导致所编码的313位氨基酸由苏氨酸变为蛋氨酸(1313M);位于第7外显子1474位的C→T,导致第492位提前出现终止密码子,截短了后面90个氨基酸。在另一个家系中检测出一个同义突变(Y454Y)。具有PINK1基因突变的患者临床特征包括发病年龄早,病情进展慢,腱反射活跃,症状波动明显,睡眠后症状减轻,对小剂量多巴制剂反应良好,未见到由左旋多巴诱导的运动障碍。结论。PINK1基因突变是常染色体隐性遗传早发性帕金森综合征的常见病因;我国大陆存在PARK6家系;PARK6具有临床异质性。

Mutation analysis of PINK1 gene in Chinese patients with autosomal recessive early-onset parkinsonism type 6

Objective To detect PINK1 gene mutations and study the clinical features in Chinese patients with autosomal recessive early-onset parkinsonism (AREP) type 6.Methods PINK1 gene mutations were detected using polymerase chain reaction (PCR) , DNA sequence analysis, and restriction enzyme digestion analysis in 11 index probands of 11 AREP families.Results Two novel point mutations in PINK1 gene, C938T in exon four,leading to substitution of a threonine for methionine codon at amino acid 313(T313M) and C1474T in exon seven introducing a stop codon at amino acid 492(R492Stop), were found in two families. In another family,a synonymous mutation (Y454Y) was detected. The clinical features in patients with PINK1 mutations included early onset,slow disease progression,hyperreflexia, diurnal fluctuations with sleep benefit, aod good response to levodopa.However, dyskinesias related to levodopa treatment were absent.Conclusion PINK1 gene mutations are a common cause of AREP.PARK6 pedigrees have been firstly identified in Chinese Mainland. Clinical heterogeneity exists in PARK6.