线粒体细胞病1例临床和基因突变分析  

Analysis of Clinic and Gene Mutation on A Infant with Mitochondrial Cytopathy

作　　者：苏玲[1] 刘丽[1] 李秀珍[1] 戴津[1] 

机构地区：[1]广州医学院附属广州市儿童医院内分泌代谢科,广州510120

出　　处：《实用儿科临床杂志》2008年第20期1576-1578,共3页Journal of Applied Clinical Pediatrics

基　　金：十一.五国家科技支撑计划项目资助(2006BAI05A07);973国家重点基础研究发展规划项目资助(2001CB510306);广东省科技厅计划项目资助(2004B36001040)

摘　　要：目的分析线粒体细胞病的临床表现、遗传学特点及其基因突变特点,从基因水平了解线粒体细胞病致病因素,并达到基因诊断和遗传咨询的目的。方法对1例线粒体细胞病患儿临床表现及实验室检查结果进行分析。提取患儿外周血基因组DNA,运用聚合酶链式反应先扩增患儿外周血线粒体基因3243、8344、8993三个热点突变所在片段,对扩增片段进行正反向序列测定,以检测突变。然后扩增已知的62个常见突变位点所在片段,对扩增片段同样进行正反向序列测定以检测突变。随机选择55例无血缘关系的健康成年人作为健康对照。结果男性患儿,出生2 d出现持续高乳酸血症、反复严重代谢性酸中毒、黄疸、肝功能异常、抽搐,头颅CT平扫示双侧大脑实质弥散性对称性低密度灶,2个月龄时死亡。线粒体3243、8344、8993三个位点均未发现突变,但细胞色素B基因存在15765 G→A突变,导致氨基酸序列340位由甘氨酸(G)转变为谷氨酸(E)。患儿母亲身体健康,外周血中亦同样存在该突变,患儿父亲及55例健康对照者皆无此突变。结论线粒体细胞病可表现为高乳酸血症、代谢性酸中毒、肝功能异常、神经系统疾病等多脏器功能损伤。线粒体细胞色素B基因15765 G→A突变可能是线粒体细胞病的一个致病突变。Objective To analyze the clinic and genetical characteristics of infant with mitochondrial cytopathy caused by mtDNA cytochrome B mutation,and to provide a practical method for gene diagnosis and genetic counseling of the disease. Methods Chnical manifestations and laboratory test results of the patient were summarized. Genomic DNA from peripheral blood was collected for genetic analysis in this patient and 55 normal controls. All fragments of 3243,8344,8993 and 62 reported common mutations in mtDNA of the patient were amplified by polymerase chain reaction（PCR） method. Forward and reverse sequencing were performed for mutation analysis. Fifty -five normal controls were used for detection of polymorphisms. Results The patient was a boy, presented as hyperlactacidemia, severe metabolic acidosis,jaundice ,hepatic malfunction and convulsion when 2 days after birth. Brain CT scan showed symmetric diffuse low - density lesions at both cerebrums. The patient was died of 2 months old. No mtDNA 3243,8344,8993 mutation were found, mtDNA 15765 G→A mutation in cytochrome B gene was detected in the patient, which lead to substitute glycine to glutamic acid at amino acid position 340. His mother had the same muta- tion in her peripheral blood but no any clinical symptoms. No such mutation was identified in father and 55 normal controls. Conclusions Mi- tocbondrial cytopathy may present as hyperlactacidemia, metabolic acidosis ,hepatic malfunction and neurological disorders, should be alerted. mtDNA 15765 G→A mutation in cytochrome B gene may cause mituchondrial cytopathy which has never been reported before in our country or abroad.

关 键 词：线粒体细胞病 线粒体细胞色素B基因 高乳酸血症 

分 类 号：R725.9[医药卫生—儿科]