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目的研究因常染色体SURF1基因突变所致Leigh综合征患儿及其家系的临床与分子遗传学特点。方法收集39例Leigh综合征患儿及其家属的外周血白细胞脱氧核糖核酸(DNA),运用聚合酶链反应(PCR)扩增SURF1基因的全部外显子序列,进行正反向序列测定检测突变,采用限制性片段长度多态性(RFLP)分析验证测序结果,并与100名健康成人对照。结果39例Leigh综合征患儿中有5例(12.8%)SURF1基因外显子7存在604G→C杂合性错义突变。5例患儿(男3例,女2例)均因智力或运动障碍于出生后8个月至9.8年来院就诊。其中3例患儿的父母接受了SURF1基因突变分析,发现双亲中一方SURF1基因存在604G→C杂合性错义突变,而另一方及健康对照的相关外显子序列未发现异常。结论我们首次报道了5例SURF1基因604G→C杂合性错义突变导致Leigh综合征的患儿及其家系,频度高达12.8%,提示该突变可能是中国人的热点突变。我们的研究将有助于今后Leigh综合征患者的诊断和遗传咨询。
Objective To investigate the clinical and molecular genetic characteristics of children with Leigh’s syndrome and their pedigree caused by the mutation of the autosomal SURF1 gene. Methods Peripheral leucocyte deoxyribonucleic acid (DNA) was collected from 39 children with Leigh’s syndrome and their relatives. All the exon sequences of SURF1 gene were amplified by polymerase chain reaction (PCR), and the positive and negative sequence analysis was used to detect the mutation The results of sequencing were verified by restriction fragment length polymorphism (RFLP) analysis and compared with 100 healthy adults. Results There were 604G → C heterozygous missense mutations in SURF1 gene exon 5 in 5 of 39 children (12.8%) with Leigh syndrome. Five children (3 males and 2 females) were admitted to hospital from 8 months to 8.9 years after birth due to mental or motor impairment. Three of the parents of the children underwent SURF1 gene mutation analysis and found that there was a 604G → C heterozygous missense mutation in the SURF1 gene of one of the parents, while no abnormality was found in the other exon and the healthy control. Conclusions We first reported 5 cases of 604G → C heterozygous missense mutation of SURF1 gene in children and their pedigrees with Leigh syndrome frequency up to 12.8%, suggesting that the mutation may be a hot mutation in Chinese. Our research will help future diagnosis and genetic counseling in patients with Leigh’s syndrome.