title: Leber's hereditary optic neuropathy is associated with the mitochondrial ND4 G11696A mutation in five Chinese families.
abstract: We report here the clinical, genetic, and molecular characterization of five Chinese families with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical ND4 G11696A mutation associated with LHON. Indeed, this mutation is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families. In fact, the occurrence of the G11696A mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Furthermore, the N405D in the ND5 and G5820A in the tRNA(Cys), showing high evolutional conservation, may contribute to the phenotypic expression of G11696A mutation in the WZ10 pedigree. However, there was the absence of functionally significant mtDNA mutations in other four Chinese pedigrees carrying the G11696A mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in these Chinese pedigrees.
authors.affiliation: School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China.
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Zhou
authors.forename: Qiping
authors.initials: Q
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Fuxin
authors.initials: F
authors.lastname: Zhao
authors.forename: Chunjie
authors.initials: C
authors.lastname: Lu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Qian
authors.forename: Yanghong
authors.initials: Y
authors.lastname: Sun
authors.forename: Fan
authors.initials: F
authors.lastname: Lu
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D019683:Penetrance; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial; C098483:NADH dehydrogenase subunit 4; D009245:NADH Dehydrogenase