一例Leigh综合征患儿的线粒体基因突变分析  

Analysis of mitochondrial gene mutations in a child with Leigh syndrome

作　　者：陈秀灵 逯军[1] Chen Xiuling;Lu Jun(Department of Pediatrics,Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan 570208 , China)

机构地区：[1]中南大学湘雅医学院附属海口医院儿科,海口 570208

出　　处：《中华医学遗传学杂志》2019年第4期318-321,共4页Chinese Journal of Medical Genetics

摘　　要：目的探讨1例临床拟诊为Leigh综合征患儿的遗传学病因。方法对患儿的临床表现及辅助检查结果进行分析,对患儿家系成员进行线粒体基因Sanger测序和多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)检测,同时对线粒体结构和功能相关的核基因进行高通量测序(next generation sequencing,NGS)。结果患儿表现为体格及运动发育落后,行走不稳、跌倒发作、双上肢抖动、肌张力增高进行性加重、抽搐,伴有口角歪斜;血生化中乳酸明显升高。头颅磁共振成像示双侧小脑半球、双侧基底节、左侧丘脑、放射冠异常信号。其母亲和哥哥无上述表现。Sanger测序显示患儿及其母亲、哥哥均携带MT-ND3 m.10191T>C异质性点突变,异质率分别是74.34%、9.73%、6.28%。MLPA检测显示患儿及其母亲、哥哥均携带MT-ND6、MTCYB-390nt异质性缺失变异。患儿及其父母、哥哥NGS测序未发现有意义的突变。结论Leigh综合征可由多种线粒体基因突变导致,这些突变可能在发病过程中具有协同作用。Objective To explore the genetic basis for a child with Leigh syndrome. Methods Clinical features and laboratory test of the patient were analyzed. Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) of the mitochondrial genome were carried out. Next generation sequencing (NGS) was used to capture and sequence nuclear genes related to mitochondrial structure and function. Results The child presented with developmental delay, unsteady gait, falling episodes, bilateral upper extremity tremor, muscle hypertonia, convulsions, and mouth angle asymmetry. Serum lactic acid was significantly increased. Cranial MRI showed abnormal signal in bilateral cerebellar hemispheres, bilateral basal ganglia, left thalamus, and corona radiata. Her mother and brother did not show any anomalies. Sanger sequencing revealed the child, her mother and brother all carried the MT-ND3 m. 10191T>C mutation, with heterogeneous rates respectively being 74.34%, 9.73%, and 6.28%. MLPA revealed heterogeneity of MT-ND6, MTCYB-390nt deletion in all three individuals. No significant mutation was found by NGS sequencing of the children, their parents and brother. Conclusion Leigh syndrome can be caused by the simultaneous existence of multiple mitochondrial genes, and multiple mutations may play a synergic role in the occurrence of the disease.

关 键 词：LEIGH综合征 MTCYB基因 线粒体复合物缺陷 

分 类 号：R725.9[医药卫生—儿科] R440[医药卫生—临床医学]