title: Very low penetrance of Leber's hereditary optic neuropathy in five Han Chinese families carrying the ND1 G3460A mutation.
abstract: We report here the clinical, genetic, and molecular characterization of five Han Chinese families with Leber's hereditary optic neuropathy (LHON). Strikingly, there were very low penetrances of visual impairment in these Chinese families, ranging from 4.2% to 22.2%, with an average of 10.2%. In particular, only 7 (4 males/3 females) of 106 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The age-at-onset for visual impairment in matrilineal relatives in these families, varied from 20 to 25 years, with an average of 21.8 years old. Molecular analysis of mitochondrial genomes identified the homoplasmic ND1 G3460A mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, C4a1, D5, F1, and R9, respectively. This suggests that the G3640A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of known secondary LHON-associated mtDNA mutations in these Chinese families. Very low penetrance of visual loss in these five Chinese pedigrees strongly indicated that the G3640A mutation was itself insufficient to develop the optic neuropathy. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G3640A mutation in those Chinese families with low penetrance of vision loss. However, nuclear modifier genes, epigenetic and environmental factors appear to be modifier factors for the phenotypic manifestation of the G3640A mutation in these Chinese families.
authors.affiliation: School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Sun
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Zhou
authors.forename: Fuxin
authors.initials: F
authors.lastname: Zhao
authors.forename: Yijian
authors.initials: Y
authors.lastname: Mao
authors.forename: Qi-ping
authors.initials: QP
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Yang
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; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D004272:DNA, Mitochondrial; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D015354:Vision, Low / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human