{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:48:38Z","timestamp":1753890518955,"version":"3.41.2"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mitochondrial intermediate peptidase, encoded by the <jats:italic>MIPEP<\/jats:italic> gene, is involved in the processing of precursor mitochondrial proteins related to oxidative phosphorylation. Only a few studies have shown that mutations in <jats:italic>MIPEP<\/jats:italic> 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 <jats:italic>MIPEP<\/jats:italic> compound heterozygous variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 &amp;gt; A (p. Tyr361Asn) and a whole deletion (Ex1-19 del), were found in the <jats:italic>MIPEP<\/jats:italic> gene, which were inherited from his healthy parents respectively. Additionally, his mitochondria DNA copy number was significantly reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We are the first to report a patient with rare <jats:italic>MIPEP<\/jats:italic> variants in China. Our findings expand the mutation spectrum of <jats:italic>MIPEP<\/jats:italic>, and provide insights into the genotype-phenotype relationship in COXPD31.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.1095882","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T04:28:51Z","timestamp":1673843331000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case report: Rare novel MIPEP compound heterozygous variants presenting with hypertrophic cardiomyopathy, severe lactic acidosis and hypotonia in a Chinese 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