A novel variant in the COX15 gene causing a fatal infantile cardioencephalomyopathy: A case report with clinical and molecular review

Eur J Med Genet. 2021 May;64(5):104195. doi: 10.1016/j.ejmg.2021.104195. Epub 2021 Mar 18.


The cytochrome c-oxidase (COX) enzyme, also known as mitochondrial complex IV (MT-C4D), is a transmembrane protein complex found in mitochondria. COX deficiency is one of the most frequent causes of electron transport chain defects in humans. Therefore, high energy demand organs and tissues are affected in patients with mutations in the COX15 gene, with variable phenotypic expressiveness. We describe the case of a male newborn with hypertrophic cardiomyopathy and serum and cerebrospinal fluid hyperlacticaemia, whose exome sequencing revealed two variants in a compound heterozygous state: c.232G > A; p.(Gly78Arg), classified as likely pathogenic, and c.452C > G; p.(Ser151Ter), as pathogenic; the former never previously described in the literature.

Keywords: COX15; Complex IV; Cytochrome c oxidase; Hyperlacticaemia; Hypertrophic cardiomyopathy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology
  • Cytochrome-c Oxidase Deficiency / genetics*
  • Cytochrome-c Oxidase Deficiency / pathology
  • Electron Transport Complex IV / genetics*
  • Heterozygote
  • Humans
  • Infant, Newborn
  • Male
  • Mitochondrial Encephalomyopathies / genetics*
  • Mitochondrial Encephalomyopathies / pathology
  • Mutation
  • Phenotype


  • COX15 protein, human
  • Electron Transport Complex IV

Supplementary concepts

  • Cardioencephalomyopathy, Fatal Infantile, due to Cytochrome C Oxidase Deficiency