Eur J Med Genet. 2023 Aug 12:104821. doi: 10.1016/j.ejmg.2023.104821. Online ahead of print.
Recently, Stenton et al. (2021) described a new, autosomal recessive inheritance pattern of Leber’s hereditary optic neuropathy (LHON) caused by missense variants in the DNAJC30 gene. The DNAJC30 c.152A > G, p.(Tyr51Cys) variant was by far the most common variant reported in patients originating from Eastern Europe, therefore, it is believed to be a founder variant in these populations. We report the first two cases of DNAJC30-linked autosomal recessive LHON in a young male and a female originating from Estonia. The patients presented severe loss of central vision and clinical features indistinguishable from mitochondrial LHON. The whole exome sequencing carried out in the male patient and the next-generation sequencing panel in the young female patient identified the same homozygous missense variant in the DNAJC30 gene. Our cases further reinforce the pathogenicity of c.152A > G, p.(Tyr51Cys) DNAJC30 variant causing autosomal recessive LHON. According to the gnomAD database, the allele frequency of this variant in the Estonian population is 0.8%, translating into a prevalence of carriers of 1:60. It is the highest among different gnomAD populations. Applying the Hardy-Weinberg equation, an estimated 92 persons in the Estonian population carry the homozygous variant c.152A > G, p.(Tyr51Cys) in DNAJC30. In patients with LHON, we advise sequencing both the DNAJC30 gene and mitochondrial DNA simultaneously.