导致Leigh综合征的SURF1基因的两个新突变  

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

作　　者：孙芳[1] 张尧[1] 杨艳玲[1] 戚豫[2] 王朝霞[3] 宋金青[1] 钱宁[1] 王丽[1] 秦炯[1] 吴希如[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院中心实验室,北京100034 [3]北京大学第一医院神经内科,北京100034

出　　处：《临床儿科杂志》2005年第8期534-537,共4页Journal of Clinical Pediatrics

基　　金：北京大学人类疾病基因研究中心科研基金(2002-01);国家自然科学基金(30471832)资助

摘　　要：目的研究 1例因常染色体 SURF1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 SURF1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. SURF1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 SURF1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.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.

关 键 词：亚急性坏死性脑脊髓病(Leigh综合征) SURFl基因 细胞色素 C氧化酶 新突变 

分 类 号：R725.9[医药卫生—儿科]