Leber's hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation.
We report here the clinical, genetic and molecular characterization of four Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age-of-onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T3394C (Y30H) mutation, which localized at a highly conserved tyrosine at position 30 of ND1, and distinct sets of mtDNA polymorphisms belonging to haplogroups D4b and M9a. The occurrence of T3394C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. However, there was the absence of functionally significant mtDNA mutations in these four Chinese pedigrees carrying the T3394C mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated T3394C mutation.
Liang
Min
M
Wenzhou Medical College, Zhejiang, China.
Guan
Minqiang
M
Zhao
Fuxing
F
Zhou
Xiangtian
X
Yuan
Meixia
M
Tong
Yi
Y
Yang
Li
L
Wei
Qi-Ping
QP
Sun
Yan-Hong
YH
Lu
Fan
F
Qu
Jia
J
Guan
Min-Xin
MX