A novel missense mutation (c.۲۱۵G>A) in two Iranian siblings with combined oxidative phosphorylation defect type ۷: A case report

Backgrounds: Combined oxidative phosphorylation defect type ۷ (COXPD۷) is a raremitochondrial disease resulting from the malfunction of the translational termination factorc۱۲orf۶۵ (MTRF-R), which leads to the disrupted mitochondrial protein synthesis. COXPD۷ ischaracterized by several phenotypes, include early onset of failure to thrive and psychomotorregression, as well as vision issues and global muscle atrophy. The prevalence is < ۱ in۱,۰۰۰,۰۰۰. So far, ten mutations have been reported in the literature to cause the disease.Materials and Methods: The proband demonstrated intellectual disability, globaldevelopmental delay, visual impairment, strabismus and scoliosis. Whole exome sequencing andfurther Sanger sequencing were carried out to confirm the mutations in the proband andadditional family members. Assessing the variant against databases such as VarSome andHGMD shed light on this novel variant.Results: The WES data identified the variant in the proband as likely pathogenic. The resultswere consistent with that of the exome sequencing, confirming the segregation of c.۲۱۵G>Awith the phenotypes.Conclusion: Here we report c.۲۱۵G>A as a novel homozygous variant in C۱۲orf۶۵. It is the firstmissense mutation to cause c۱۲orf۶۵-related diseases, suggesting a loss of function mechanismmight have led the multi-systemic phenotypes.

Keywords:

COXPD۷ , C۱۲orf۶۵ , WES , Missense mutation , Mitochondrial disorder