title: The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a Chinese family with Leber's hereditary optic neuropathy and hearing loss.
abstract: We report here the clinical, genetic and molecular characterization of one three-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON) and hearing loss. Four of 14 matrilineal relatives exhibited the moderate central vision loss at the average age of 12.5 years. Of these, one subject exhibited both LHON and mild hearing impairment. Sequence analysis of the complete mitochondrial genomes in the pedigree showed the presence of homoplasmic LHON-associated ND6 T14484C mutation, deafness-associated 12S rRNA A1555 mutation and 47 other variants belonging to Eastern Asian haplogroup H2. None of other mitochondrial variants was evolutionarily conserved and functional significance. Therefore, the coexistence of the A1555G mutation and T14484C mutations in this Chinese family indicate that the A1555G mutation may play a synergistic role in the phenotypic manifestation of LHON associated ND6 T14484C mutation. However, the incomplete penetrance of vision and hearing loss suggests the involvement of nuclear modifier genes and environmental factors in the phenotypic expression of these mtDNA mutations.
authors: Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078, China.
authors: Qi-Ping
authors: QP
authors: Wei
authors: Xiangtian
authors: X
authors: Zhou
authors: Li
authors: L
authors: Yang
authors: Yan-Hong
authors: YH
authors: Sun
authors: Jian
authors: J
authors: Zhou
authors: Guang
authors: G
authors: Li
authors: Robert
authors: R
authors: Jiang
authors: Fan
authors: F
authors: Lu
authors: Jia
authors: J
authors: Qu
authors: Min-Xin
authors: MX
authors: Guan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D034381:Hearing Loss / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D012335:RNA, Ribosomal / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase