Mitochondrial ND6 T14502C variant may modulate the phenotypic expression of LHON-associated G11778A mutation in four Chinese families.
We report here the clinical, genetic, and molecular evaluations of four Han Chinese families with Leber's hereditary optic neuropathy. Thirty-one (20 males/11 females) of 83 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual impairment. The average age-of-onset of vision loss was 22years old. Strikingly, these penetrances of visual impairment in these Chinese families were higher than those in other 11 Chinese pedigrees carrying the only ND4 G11778A mutation. Molecular analysis identified the known G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M10a and M7c2. Of these, the T14502C mutation caused the substitution of a highly conserved isoleucine for valine at position 58 in ND6. This mutation has been associated with LHON in other Chinese families with very low penetrance of LHON. Thus, the deficient activities of complex I, caused by G11778A mutation, would be worsened by the T14502C mutation in these four Chinese families. As a result, mitochondrial dysfunctions would lead to the high penetrance and expressivity of visual loss in these Chinese families carrying both G11778A and T14502C mutations than other 11 Chinese families carrying only G11778A mutation. These data suggested that the T14502C variant may modulate the phenotypic manifestation of the G11778A mutation in these Chinese pedigrees.
Zhang
Juanjuan
J
School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, China.
Zhou
Xiangtian
X
Zhou
Jian
J
Li
Chengwu
C
Zhao
Fuxin
F
Wang
Yan
Y
Meng
Yanzi
Y
Wang
Jiying
J
Yuan
Meixia
M
Cai
Wanshi
W
Tong
Yi
Y
Sun
Yan-Hong
YH
Yang
Li
L
Qu
Jia
J
Guan
Min-Xin
MX
D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D055815:Young Adult
C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase