COA6基因新发变异致婴儿细胞色素c氧化酶缺陷致心脑肌病4型1例报告并文献复习

目的提高对婴儿细胞色素c氧化酶缺陷致心脑肌病4型(CEMCOX 4)临床表型及基因型的认识。方法回顾分析1例婴儿CEMCOX4患儿的临床资料并复习相关文献。结果女性患儿,5日龄,出生后即出现呼吸困难;多次血气分析示乳酸增高;心脏彩超示肥厚型心肌病,双侧心室流出道梗阻。全外显子测序发现患儿COA6基因存在c.411_412insAAAG纯合变异,导致从第140个赖氨酸开始的氨基酸合成发生改变,并在改变后的第4个氨基酸终止(p.Lys 140 ArgfsTer 4),可能致蛋白质功能受到严重影响。家系验证示父母均携带c.411_412 insAAAG杂合变异。该变异未曾见报道。文献复习提示婴儿CEMCOX4多表现为乳酸性酸中毒、肌张力低下及肥厚性心肌病,致病基因的纯合变异较复合杂合变异预后更差。结论报道婴儿CEMCOX4病例,并发现新的COA6基因变异,扩充了COA6基因变异谱。

Infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency-4 caused by a novel mutation of COA6 gene:a case report and literature review

Objective To explore the clinical phenotype and genotype of infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency-4(CEMCOX4).Methods The clinical data of an infantile CEMCOX 4 was analyzed retrospectively and the related literature was reviewed.Results The 5-day-old female infant presented with dyspnea immediately after birth.Repeated blood gas analysis showed an increase in lactic acid.Cardiac color Doppler ultrasonography showed hypertrophic cardiomyopathy with bilateral ventricular outflow tract obstruction.A homozygous mutation of c.411_412 insAAAG in COA6 gene was detected by whole exon sequencing and the mutation resulted in the change of amino acid synthesis starting from the 140 th lysine and ending at subsequent 4 th amino acid after the change(p.Lys140 ArgfsTer4).It may seriously affect the protein function.Family pedigree verification showed that both parents carried the c.411_412insAAAG heterozygous variation.This mutation has not been reported.Literature review showed that infantile CEMCOX4 usually presented with lactic acidosis,hypotonia and hypertrophic cardiomyopathy,and the prognosis of homozygous variation is worse than that of compound heterozygous variation.Conclusions One case of infant CEMCOX4 was reported.A new mutation in COA6 gene was discovered,which expanded the COA6 gene mutation spectrum.