title: Co-segregation of the T1095C with the A1555G mutation of the mitochondrial 12S rRNA gene in a patient with non-syndromic hearing loss.
abstract: We reported here the clinical and molecular characterization of a Chinese subject with childhood-onset hearing impairment. Clinical evaluations showed that the patient suffered from profound and non-syndromic sensorineural hearing loss with flat configurations. Sequence analysis of the mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes led to the identification of double deafness-associated mutations of A1555G and T1095C in the 12S rRNA gene which apparently in the homoplasmic forms. In additional, there was no other functionally significant nucleotide variants found in this subject. As previous studies have indicated that the A1555G mutation was a primary contributing factor underlying the development of deafness but not sufficient to produce clinical phenotype, the co-segregation of two mitochondrial DNA mutations raises the possibility that the T to C transition at position 1095 plays a role in the phenotypic expression of deafness-associated A1555G mutation. Actually, the T1095C mutation disrupted an evolutionarily conserved base-pair at stem-loop of helix 25 of 12S rRNA, resulting in impaired translation in mitochondrial protein synthesis and a significant reduction of cytochrome c oxidase activity. As a result, it may enhance the biochemical defect in patient carrying the A1555G mutation, thus changing the age of onset and the severity of hearing impairment.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Dachun
authors.initials: D
authors.lastname: Dai
authors.forename: Yajie
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Chen
authors.forename: Qinjun
authors.initials: Q
authors.lastname: Wei
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Guangqian
authors.initials: G
authors.lastname: Xing
mesh_terms: D000293:Adolescent; D044466:Asian People; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D050259:Genes, Mitochondrial; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics*; D012362:RNA, Transfer, Ser / Q000235:genetics
chemical_list: D017630:Connexins; D012335:RNA, Ribosomal; D012362:RNA, Transfer, Ser; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26