[Leber's hereditary optic neuropathy is associated with the mitochondrial G11696A mutation in two Chinese families].
OBJECTIVE
To report the clinical, genetic, and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy (LHON).


METHODS
Ophthalmological examinations showed that only probands in two families exhibited visual loss at the age of 10 and 17 years respectively. The entire mitochondrial genome of two probands was PCR amplified in 24 overlapping fragments using sets of oligonucleotide primers.


RESULTS
Mutational analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T144484 mutations but the presence of homoplastic LHON associated ND4 G11696A mutation, which was present in one out of 167 Chinese healthy controls.


CONCLUSIONS
Sequence analysis of the complete mitochondrial genomes in two pedigrees showed the distinct sets of mtDNA polymorphisms, belonging to Eastern Asian haplogroup D4. The incomplete penetrance of visual loss and the presence of one in 167 controls suggested that this mutation itself is insufficient to produce a clinical phenotype and other modifier factors play a role in the phenotypic manifestation. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in two Chinese pedigrees.
Zhao
Fu-xin
FX
Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang, 325035 PR China.
Zhou
Xiang-tian
XT
Qu
Jia
J
Wei
Qi-ping
QP
Tong
Yi
Y
Yang
Li
L
Lv
Jian-xin
JX
Guan
Min-xin
MX
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
D004272:DNA, Mitochondrial