Low penetrance of Leber's hereditary optic neuropathy in ten Han Chinese families carrying the ND6 T11484C mutation.
BACKGROUND
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder. The purpose of this investigation is to understand the role of mitochondrial haplotypes in the development of LHON associated with ND6 T14484C mutation in Chinese families.


METHODS
One hundred fourteen subjects from ten Han Chinese families with LHON were studied by the clinical and genetic evaluation as well as molecular and biochemical analyses of mitochondrial DNA (mtDNA).


RESULTS
Clinical evaluation revealed that ten families exhibited extremely low penetrance of visual impairment, with an average of 10%. In particular, ten (8 males/2 females) of 114 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The average age-of-onset of vision loss was 19 years old. Molecular analysis of mitochondrial DNA (mtDNA) identified the homoplasmic T14484C mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, D4, D4g1b, G3a2, R11, R11a and Z3, respectively. However, there was the absence of secondary LHON-associated mtDNA mutations in these ten Chinese families.


CONCLUSIONS
The low penetrance of vision loss in these Chinese pedigrees strongly indicated that the T14484C mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the T14484C mutation in those Chinese families with low penentrace of vision loss. However, nuclear modifier genes and environmental factors appear to be modifier factors for the phenotypic manifestation of the T14484C mutation in these Chinese families.
Qu
Jia
J
School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China. jqu@wzmc.net
Zhou
Xiangtian
X
Zhao
Fuxin
F
Liu
Xiaoling
X
Zhang
Minglian
M
Sun
Yan-Hong
YH
Liang
Min
M
Yuan
Meixia
M
Liu
Qi
Q
Tong
Yi
Y
Wei
Qi-Ping
QP
Yang
Li
L
Guan
Min-Xin
MX
D044466:Asian People / Q000235:genetics; D002681:China; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D014792:Visual Acuity; D014794:Visual Fields
D004272:DNA, Mitochondrial; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase