导致 Leigh综合征的 SURF1基因的两个新突变

目的 研究1例因常染色体SURFl基因新突变所致Leigh综合征患者的临床及遗传学的特点。方法 提取患儿外周血白细胞DNA，先进行线粒体基因热点突变的筛查，然后运用聚合酶链式反应扩增SURFl基因的全部外显子序列，进行正反向序列测定以检测突变。103名无关健康个体为正常对照组。结果 患儿从1岁2个月起出现进行性运动智力倒退，无力，喂养困难，2岁3个月时死于呼吸衰竭。其兄临床经过类似，2岁时死亡。线粒体基因筛查排除8993C〉T、3243A〉G、8344A〉G突变。SURFl基因序列测定显示该患者存在复合杂合性缺失，分别为外显子7第622位缺失A（622delA）和第653～654位缺失CT（653－654delCT）。结论　SURF1基因参与调控细胞色素C氧化酶复合物的组装，而细胞色素C氧化酶复合物缺陷是导致Leigh综合征的主要原因。本研究发现了SURFl基因622delA以及653-654delCT两个杂合性缺失为2个新突变，明确了患者的病因，并进一步充实了人类Leigh综合征致病基因库，将有助于今后Leigh综合征家系的遗传咨询。

Two novel SURF1 mutations in a Chinese patient died from Leigh syndrome

Objective Leigh syndrome is a severe disorder with early_onset progressive neurodegeneration due to mitochondrial oxidative phosphorylation defect.The study aimed to detect the SURF1 gene defects in a Chinese patient died from Leigh sydrome and review the clinical feature.Methods Genomic NDA from peripheral blood leucocytes was collected for genetic analysis in this patient and 103 normal controls.All nine exons of SURF1 were amplified by polymerase chain reaction(PCR)method.Forward and reverse sequencing were performed for mutation analysis.Results This patient developed psychomotor retardation from the age of 14 months and died from respiratory failure at the age of 27 months.His elder brother had similar clinical manifestations and died at the age of 24 months.Mitochondrial DNA mutations 8993C>T,3243A>G were not found and two compound heterozygous deletions of 622delA and 653-654delCT on exon 7 of SURF1 were detected in this patient,in the meanwhile no mutations were identified in the normal controls.Conclusions We report first a Chinese patient with Leigh syndrome due to 622delA and 653-654delCT heterozygous deletions in SURF1 gene.Cytochrome C oxidase(COX) deficiency due to SURF1 gene defects is one of the most common causes of Leigh syndrome.Our study will be helpful for the genetic consulation of the family and for the research of Leigh syndrome.