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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 To study the clinical and genetics characteristics of one case of Leigh syndrome caused by a new mutation of the autosomal gene SURF1. Methods The peripheral blood leukocyte DNA in children was extracted. The mitochondrial DNA was first screened by hot spot mutation. Then all the exons of SURF1 gene were amplified by polymerase chain reaction (PCR), and the positive and negative sequences were determined to detect the mutation. 103 unrelated healthy individuals as normal control group. Results From the age of 1 year and 2 months, children with progressive exercise retarded, weakness, feeding difficulties, 2-year-old died of respiratory failure at 3 months. His brother after a similar clinical death at the age of 2. Mitochondrial gene screening excluded 8993C> T, 3243A> G, 8344A> G mutations. SURF1 gene sequence analysis showed that there was compound heterozygosity deletion in this patient, which was 622 (622delA) in exon 7, and 653-654delCT (653-654delCT) in exon 7, respectively. Conclusion SURF1 gene is involved in the regulation of cytochrome C oxidase complex assembly, and cytochrome C oxidase complex defect is the leading cause of Leigh syndrome. In this study, we found two novel mutations in the 622delA and 653-654delCT of SURF1 gene, identified two new mutations, clarified the etiology of the patients and further enriched the causative gene pool of human Leigh syndrome, which will contribute to the future Leigh syndrome Family genetic counseling.