Stenton Sarah L, Tesarova Marketa, Sheremet Natalia L, Catarino Claudia B, Carelli Valerio, Ciara Elżbieta, Curry Kathryn, Engvall Martin, Fleming Leah R, Freisinger Peter, Iwanicka-Pronicka Katarzyna, Jurkiewicz Elżbieta, Klopstock Thomas, Koenig Mary K, Kolářová Hana, Kousal Bohdan, Krylova Tatiana, La Morgia Chiara, Nosková Lenka, Piekutowska-Abramczuk Dorota, Russo Sam N, Stránecký Viktor, Tóthová Iveta, Träisk Frank, Prokisch Holger
Institute of Human Genetics, School of Medicine, Technische Universität München, München, Germany.
Institute of Neurogenomics, Helmholtz Zentrum München, München, Germany.
Brain. 2022 Jun 3;145(5):1624-1631. doi: 10.1093/brain/awac052.
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.
近期关于双等位基因DNAJC30变异体与Leber遗传性视神经病变（LHON）和Leigh综合征的报道，挑战了LHON仅通过母系遗传的长期假设，并拓宽了Leigh综合征的遗传谱，Leigh综合征是最常见的儿童线粒体疾病。在此，我们对来自26个家庭的28名此前未报道的个体进行了特征分析，这些个体携带纯合的DNAJC30 p.Tyr51Cys始祖变异体，其中24人表现为LHON，2人表现为Leigh综合征，2人仍无症状。这组未报道的变异体携带者证实了该纯合变异体存在性别依赖性不完全外显率，因为疾病明显以男性为主，且有无症状纯合变异体携带者的报道。与母系遗传疾病的报道数据相比，常染色体隐性遗传的LHON患者疾病发病年龄更早，艾地苯醌治疗和视力自发恢复率更高。此外，另外两名儿童期或成人期发病的Leigh综合征患者的报道进一步证明了DNAJC30与Leigh综合征的关联，此前仅在一例儿童期发病病例中有报道。
