In 6 patients from 4 families, including 2 unrelated Kurdish patients (families 1 and 2), 2 German sibs (family 3), and 2 Turkish sibs (family 4), with combined oxidative phosphorylation deficiency-53 (COXPD53; 619423), Lausberg et al. (2021) identified homozygosity for a 1-bp deletion (c.298delC, NM_153689.6) in the C2ORF69 gene, resulting in a frameshift and premature termination (Gln100SerfsTer18). The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In lymphocytes from one patient, C2ORF69 RNA was at comparable levels to controls, but the protein was absent, indicating instability of the truncated protein.
In 5 patients from 3 families with COXPD53, including 2 Kurdish Turkish sibs (family 1), 2 Iranian sibs (family 4), and an Iraqi patient (family 7), all born of consanguineous parents, Wong et al. (2021) identified homozygosity for the c.298delC mutation in the C2ORF69 gene. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The mutation was not present in the gnomAD (v.2.1.1 and v.3.1) or TOPmed databases or in an in-house database consisting of more than 50,000 genomes/exomes. In family 7, the patient had 4 similarly affected deceased sibs and 1 similarly affected living sib who were not tested for the mutation.
