title: Mitochondrial haplogroup M9a specific variant ND1 T3394C may have a modifying role in the phenotypic expression of the LHON-associated ND4 G11778A mutation.
abstract: We report here the clinical, genetic and molecular characterization of four Han Chinese families with Leber's hereditary optic neuropathy (LHON). The penetrances of optic neuropathy in these Chinese pedigrees were 38%, 38%, 44% and 56%. This observation is in contrast with the previously identified 14 Chinese families with very low penetrance of LHON. The age-at-onset for visual impairment in matrilineal relatives in these Chinese families varied from 18 to 30years. Furthermore, the ratios between affected male and female matrilineal relatives in these families were 3:0, 3:0, 3:1 and 2:3, respectively. Molecular analysis of mitochondrial genomes identified the known ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M9a. Of these, the ND1 T3394C mutation caused the substitution of a highly conserved histidine for tyrosine (Y30H) at amino acid position 30. This mutation was associated with LHON in other families with low penetrance of optic neuropathy and other clinical abnormalities. The presence of both G11778A and T3394C mutations appears to contribute to higher penetrance of optic neuropathy in these four Chinese families than other Chinese families carrying only the G11778A mutation. Therefore, the mitochondrial haplogroup M9a specific variant T3394C may modulate the phenotypic manifestation of LHON-associated G11778A mutation in these Chinese pedigrees.
authors: Department of Ophthalmology, Xingtai Eye Hospital, Xingtai, Hebei, China.
authors: Minglian
authors: M
authors: Zhang
authors: Xiangtian
authors: X
authors: Zhou
authors: Chengwu
authors: C
authors: Li
authors: Fuxin
authors: F
authors: Zhao
authors: Juanjuan
authors: J
authors: Zhang
authors: Meixia
authors: M
authors: Yuan
authors: Yan-Hong
authors: YH
authors: Sun
authors: Jingzheng
authors: J
authors: Wang
authors: Yi
authors: Y
authors: Tong
authors: Min
authors: M
authors: Liang
authors: Li
authors: L
authors: Yang
authors: Wanshi
authors: W
authors: Cai
authors: Lifei
authors: L
authors: Wang
authors: Jia
authors: J
authors: Qu
authors: Min-Xin
authors: MX
authors: Guan
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D015354:Vision, Low / Q000235:genetics
chemical_list: D009245:NADH Dehydrogenase