title: Novel nucleotide changes in mutational analysis of mitochondrial 12SrRNA gene in patients with nonsyndromic and aminoglycoside-induced hearing loss.
abstract: Mitochondria have essential role in cellular energy metabolism and defects in their function lead to many metabolic diseases. Mitochondrial DNA (mtDNA) mutations have been associated with number diseases such as nonsyndromic and aminoglycoside-induced hearing loss. Mutational screening of entire 12SrRNA and tRNA (ser (UCN)) genes in 107 unrelated Iranian patients with amino glycoside-induced and nonsyndromic bilateral hearing loss by direct sequencing analysis method were performed. Twenty different homoplasmic sequence variants were identified; including fifteen common polymorphisms, two putatively pathogenic variants: m.921T>C and m.1005T>C, one 12SrRNA sequence variant m.739C>T and two nucleotides substitution; m.1245T>C and m.1545T>C. Deafness-associated mutation, m.1555A>G, was not found. In our patients we found the mutation 1005 was associated with R haplogroup. These finding show that m.1555A>G mutation is not important in our population. Nucleotide change, m.739C>T, previously reported with very low frequency. We suggested the variation of two nucleotides 1245 and 1545 that localized at conserved site of 12SrRNA may be new candidate for amino glycoside-induced and nonsyndromic hearing impairment associated mutations. However, aminoglycoside exposure is a risk factor for clinical phenotype appearance of these mutations.
authors.affiliation: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Dowlati
authors.forename: Pupak
authors.initials: P
authors.lastname: Derakhshandeh-Peykar
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Mohammad
authors.initials: M
authors.lastname: Farhadi
authors.forename: Azadeh
authors.initials: A
authors.lastname: Shojaei
authors.forename: Masoomeh
authors.initials: M
authors.lastname: Fallah
authors.forename: Esmaiil
authors.initials: E
authors.lastname: Mohammadi
authors.forename: Ardavan
authors.initials: A
authors.lastname: Tajdini
authors.forename: Shima
authors.initials: S
authors.lastname: Arastoo
authors.forename: Javad
authors.initials: J
authors.lastname: Tavakkoly-Bazzaz
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D050259:Genes, Mitochondrial; D006239:Haplotypes; D034381:Hearing Loss / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics*; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S