ClinVar

In 3 sisters, born of unrelated parents of Iraqi-Jewish descent, with coenzyme Q10 deficiency-9 (COQ10D9; 619028), Malicdan et al. (2018) identified a homozygous 9,590-bp duplication (chr12:120,940,098-120,949,687, GRCh37) in the COQ5 gene. The duplication, which was found by detailed genetic analysis and confirmed by Sanger sequencing, segregated with the disorder in the family. The duplication spanned the last 4 exons of the COQ5 gene, but did not alter the open reading frame: it was located about 1 kb beyond the DNA sequence that encodes the 3-prime untranslated region. Patient fibroblasts and leukocytes, and skeletal muscle tissue from 1 patient, had significantly decreased COQ5 mRNA and protein levels compared to controls. Cultured fibroblasts from 1 patient showed a defect in mitochondrial complex II+III activity and abnormal oxygen consumption, suggesting that the mutation had an adverse effect on mitochondrial respiration. Homozygosity for the variant was not found in 92 healthy individuals from the same ethnic background; however, there were 3 heterozygous carriers, yielding a minor allele frequency of about 1.5%.