title: Mitochondrial DNA mutation m.3635G>A may be associated with Leber hereditary optic neuropathy in Chinese.
abstract: Leber hereditary optic neuropathy (LHON) was the first disease to be linked to the presence of a mitochondrial DNA (mtDNA) mutation. Nowadays over 95% of LHON cases are known to be caused by one of three primary mutations (m.11778G>A, m.14484T>C, and m.3460G>A). Reports for other (rare) primary mutations in LHON patients are not infrequent. Among those is the mutation m.3635G>A in the MT-ND1 gene which was reported to be pathogenic in a Russian LHON family. In this study, we report on a Chinese family with clinical features of LHON but without any of the three well-known primary mutations. Analysis of the complete mitochondrial genome in the proband revealed the presence of m.3635G>A and m.6228C>T, along with a full array of other variants that suggest the haplogroup M7b1. Evolutionary analysis indicates that site 3635, but not 6228, is highly conserved in vertebrates. Protein secondary-structure modeling for the MT-ND1 protein harboring amino acid change S110N indicates that mutant m.3635G>A decreases the protein hydrophobicity. Our current observations provide further support for a pathogenic role of m.3635G>A in patients with LHON.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D017433:Protein Structure, Secondary
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human