ND1 G3635A mutation in the mitochondrial DNA in three Chinese pedigrees of Leber's hereditary optic neuropathy

Abstract

Objective To screen mitochondrial DNA mutations in 3 Chinese pedigrees with Leber's hereditary optic neuropathy (LHON) carrying the ND1 G3635A mutation. Methods88 members (53maternal relatives and 35 paternal relatives)in 3 pedigrees were enrolled. The ophthalmologic examinations were performed for all members, including visual acuity (standard logarithmic visual acuity charts), fundus photography (Canon fundus camera), visual field (Humphrey Visual Field Analyzer), color vision (Yu zhiping color vision plate), and visual evoked potentials (Roland Consult RETI port gamma, flash VEP).16 members had LHON, 72 members did not have LHON. 135 healthy people from Wenzhou were included as the control group. Genomic DNA was extracted from peripheral blood leukocytes of all subjects. G3635A mutation was screened by PCR-amplification of mitochondrial DNA for all subjects. Mitochondrial haplotypes and other mutations in the entire mitochondrial genome were also determined by PCR using 24pairs of primers for the probands. ResultsAnalysis of mitochondrial DNA (mtDNA) in 3 pedigrees revealed the presence of ND1 G3635A mutation in 3 probands and all maternal relatives, but not in paternal relatives and healthy controls. Proband's haplogroup belong to East Asia group N9a3, D4, and R11a. In addition to the G3635A mutation, probands also had other variants including 12 variants in D-loop region, 6variants in RNA gene, and 36 variants in protein-encoding gene. ConclusionsG3635A mutation was identified in probands and maternal relatives of 3 pedigrees of LHON. It showed that G3635A mutation was the pathogenic molecular basis for those patients. Key words: Optic atrophy, hereditary, Leber/etiology; DNA, nitochondrial; Mutation