title: Confirmation of the mitochondrial ND1 gene mutation G3635A as a primary LHON mutation.
abstract: We report the clinical and genetic characterization of two Chinese LHON families who do not carry the primary LHON-mutations. Mitochondrial genome sequence analysis revealed the presence of a homoplasmic ND1 G3635A mutation in both families. In Family LHON-001, 31 other variants belonging to the East Asian haplogroup R11a were identified and in Family LHON-019, 37 other variants belonging to the East Asian haplogroup D4g were determined. The ND1 G3635A mutation changes the conversed serine110 residue to asparagine. This mutation has been previously described in a single Russian LHON family and has been suggested to contribute to increased LHON expressivity. In addition, a mutation in cytochrome c oxidase subunit II at C7868T (COII/L95F) may act in synergy with G3635A, increasing LHON expressivity in Family LHON-001, which had a higher level of LHON penetrance than Family LHON-019. In summary, the G3635A mutation is confirmed as a rare primary pathogenic mutation for LHON.
authors.affiliation: Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, China. Julian_yang@mail.fjmu.edu.cn
authors.forename: Juhua
authors.initials: J
authors.lastname: Yang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Dinggou
authors.initials: D
authors.lastname: Huang
authors.forename: Wentong
authors.initials: W
authors.lastname: Qiu
authors.forename: Shuliu
authors.initials: S
authors.lastname: Zhuang
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D055815:Young Adult
chemical_list: D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human