Wang Ling, Lu Pengtao, Yin Jie, Xu Kangkang, Xiang Dandan, Zhang Zhongman, Zhang Han, Zheng Bixia, Zhou Wei, Wang Chunli, Yang Shiwei
Department of Cardiology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Front Cardiovasc Med. 2023 Jan 16;9:1095882. doi: 10.3389/fcvm.2022.1095882. eCollection 2022.
Mitochondrial intermediate peptidase, encoded by the gene, is involved in the processing of precursor mitochondrial proteins related to oxidative phosphorylation. Only a few studies have shown that mutations in can cause combined oxidative phosphorylation deficiency-31 (COXPD31), an autosomal recessive multisystem disorder associated with mitochondrial dysfunction. We report herein a rare case of an 8-month-old boy in China with hypertrophic cardiomyopathy (HCM), severe lactic acidosis, and hypotonia caused by novel compound heterozygous variants.
Trio-whole-exome sequencing and copy number variation sequencing were performed to identify mutated genetic loci. Sanger sequencing and quantitative real-time PCR were used to validate the candidate single nucleotide variants and copy number variants, respectively.
The proband was an 8-month-old boy with HCM, severe lactic acidosis, and hypotonia who died 2 months after his first admission. Two novel compound heterozygous variants, c.1081T > A (p. Tyr361Asn) and a whole deletion (Ex1-19 del), were found in the gene, which were inherited from his healthy parents respectively. Additionally, his mitochondria DNA copy number was significantly reduced.
We are the first to report a patient with rare variants in China. Our findings expand the mutation spectrum of , and provide insights into the genotype-phenotype relationship in COXPD31.
由该基因编码的线粒体中间肽酶参与与氧化磷酸化相关的前体线粒体蛋白的加工过程。仅有少数研究表明该基因突变可导致联合氧化磷酸化缺陷31型（COXPD31），这是一种与线粒体功能障碍相关的常染色体隐性多系统疾病。我们在此报告中国一名8个月大患有肥厚型心肌病（HCM）、严重乳酸酸中毒和低张力的男孩的罕见病例，其病因是新的复合杂合变异。
进行三联全外显子测序和拷贝数变异测序以鉴定突变的基因位点。分别使用桑格测序和定量实时PCR验证候选单核苷酸变异和拷贝数变异。
先证者是一名8个月大患有HCM、严重乳酸酸中毒和低张力的男孩，首次入院后2个月死亡。在该基因中发现两个新的复合杂合变异，即c.1081T>A（p.Tyr361Asn）和一个全缺失（Ex1-19 del），分别遗传自他健康的父母。此外，他的线粒体DNA拷贝数显著减少。
我们是首次在中国报告一名具有罕见该基因变异的患者。我们的发现扩展了该基因的突变谱，并为COXPD31的基因型-表型关系提供了见解。
