DNAJC30 defect: a frequent cause of recessive Leber hereditary optic neuropathy and Leigh syndrome

Stenton, Sarah L.; Tesarova, Marketa; Sheremet, Natalia L.; Catarino, Claudia; Carelli, Valerio; Ciara, Elzbieta; Curry, Kathryn; Engvall, Martin; Fleming, Leah R.; Freisinger, Peter; Iwanicka-Pronicka, Katarzyna; Jurkiewicz, Elzbieta; Klopstock, Thomas; Koenig, Mary K.; Kolarova, Hana; Kousal, Bohdan; Krylova, Tatiana; La Morgia, Chiara; Noskova, Lenka; Piekutowska-Abramczuk, Dorota; Russo, Sam N.; Stranecky, Viktor; Tothova, Iveta; Traisk, Frank und Prokisch, Holger (2022): DNAJC30 defect: a frequent cause of recessive Leber hereditary optic neuropathy and Leigh syndrome. In: Brain, Bd. 145, Nr. 5: S. 1624-1631

Abstract

The recent description of biallelic DNAJC30 variants in Leber hereditary optic neuropathy (LHON) and Leigh syndrome challenged the longstanding assumption for LHON to be exclusively maternally inherited and broadened the genetic spectrum of Leigh syndrome, the most frequent paediatric mitochondrial disease. Herein, we characterize 28 so far unreported individuals from 26 families carrying a homozygous DNAJC30 p.Tyr51Cys founder variant, 24 manifesting with LHON, two manifesting with Leigh syndrome, and two remaining asymptomatic. This collection of unreported variant carriers confirms sex-dependent incomplete penetrance of the homozygous variant given a significant male predominance of disease and the report of asymptomatic homozygous variant carriers. The autosomal recessive LHON patients demonstrate an earlier age of disease onset and a higher rate of idebenone-treated and spontaneous recovery of vision in comparison to reported figures for maternally inherited disease. Moreover, the report of two additional patients with childhood- or adult-onset Leigh syndrome further evidences the association of DNAJC30 with Leigh syndrome, previously only reported in a single childhood-onset case. Stenton et al. describe 28 individuals with LHON, Leigh syndrome or asymptomatic carriage of a pathogenic founder variant in the autosomal recessive mitochondrial disease gene DNAJC30. The findings confirm sex-dependent incomplete penetrance, frequent occurrence of recessive LHON, and the association of DNAJC30 with Leigh syndrome.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0006-8950
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198