关键词: Leber遗传性视神经病变, 线粒体, 突变, 视力损害, tRNA

Abstract: We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNA^Ala C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNA^Ala, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in vis-ual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNA^Ala C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of func-tional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phe-notypic manifestation of the tRNA^Ala C5601T mutation in the seven Chinese families.

Key words: Leber’s hereditary optic neuropathy, mitochondrial, mutation, visual impairment, tRNA