SURF1基因突变导致Leigh综合征家系1例

Leigh综合征是一种由于线粒体氧化磷酸化障碍所导致的严重退行性脑病。常染色体SURF1基因突变所致细胞色素C氧化酶缺乏是导致Leigh综合征的常见原因,国外已报道多种突变类型。该研究回顾了1例SURF1基因604G>C杂合性错义突变所致中国人Leigh综合征患者及其家系的临床与遗传学特点。患者,女, 9个月起病,表现为喂养困难,营养不良,进行性运动倒退,肌张力低下,眼震。17个月时来院就诊, 23个月时死于呼吸衰竭。脑MRI显示双侧基底节对称性损害,脑干、小脑萎缩。聚合酶链式反应扩增SURF1基因的全部外显子,进行序列测定及限制性片断长度多态性分析均显示患者及其母亲、舅舅的SURF1基因的外显子7存在一个604G>C杂合性错义突变,其父亲及正常对照的相关外显子序列未发现异常。该研究首次报道了1例中国人群中由于SURF1基因604G>C杂合性错义突变导致的Leigh综合征及其家系,不仅明确了病因,亦将有助于今后对患者家系的遗传咨询。

604G>C heterozygous mutation of SURF1 identified in a Chinese pedigree with Leigh syndrome

Leigh syndrome is a severe early-onset progressive neurodegenerative disorder due to mitochondrial oxidative phosphorylation defects. Nuclear SURF1 mutations are the main causes of Cytochrome C oxidase deficiency resulting in Leigh syndrome. This study reviewed the clinical and genetic characteristics of a Chinese girl with Leigh syndrome due to 604G>C heterozygous mutation in SURF1. The female patient fell ill at age of 9 months, manifesting with feeding difficulty, malnutrition, progressive motor degeneration, hypotonia and nystagmus. She was hospitalized at 17 months and died of respiratory failure at 23 months. Her blood lactate and pyruvate levels detected during admission were significantly increased. Brain MR imaging showed characteristic focal, bilateral lesions in brain stem, thalamus, and basal ganglia. Brain stem and cerebellar atrophy were also found. Mitochondrial gene mutations were excluded. All of the exons of SURF1 amplified by polymerase chain reaction (PCR) sequencing and PCR-Restriction Fragment Length Polymorphism (RFLP) showed a 604G>C heterozygous mutation of SURF1 in the proband. Her mother and uncle had the mutations of SURF1 but no mutations were identified in her father and in 100 normal controls aged 14-18 years. This is the first reported case in China of Leigh syndrome due to 604G>C heterozygous mutation in SURF1 and it will be helpful for the diagnosis of Leigh syndrome and genetic counseling of the patient′s pedigree in future.