Novel A14841G mutation is associated with high penetrance of LHON/C4171A family.
We report the clinical and genetic characterization of a Chinese LHON family carrying an ND1/C4171A mutation. This family has high penetrance of visual impairment and extremely low frequency of vision recovery, which is in marked contrast to previously reported results for Korean LHON families with the same mutation. Sequence analysis of the complete mtDNA in the partially defined East Asian haplogroup N9a1 revealed the presence of 29 other variants. A novel heteroplasmic A14841G mutation, one of the variants with a serine substituted for a highly conserved asparagine at amino acid 32 of Cytochrome b (Cytb), may play a synergistic role with the C4171A mutation, leading to significantly different clinical manifestations of LHON among these families. The study further confirmed that C4171A was a rare primary LHON mutation, and the mtDNA background could also contribute to the clinical manifestation of the LHON/C4171A mutation.
Yang
Juhua
J
Biomedical Engineering Center, Fujian Medical University, Fuzhou, Fujian, China. Julian_yang@mail.fjmu.edu.cn
Zhu
Yihua
Y
Chen
Lu
L
Zhang
Hongxing
H
Tong
Yi
Y
Huang
Dinggou
D
Zhang
Zhiqiang
Z
Chen
Shi
S
Han
Xiaoli
X
Ma
Xu
X
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People; D001483:Base Sequence; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance
D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human