title: Mutation analysis of mitochondrial DNA 12SrRNA and tRNASer(UCN) genes in non-syndromic hearing loss patients.
abstract: Specific mitochondrial DNA (mtDNA) mutations in 12SrRNA and tRNASer(UCN) cause non-syndromic hearing loss (NSHL). In this study, we screened 466 hearing loss (HL) patients, negative for GJB2 mutations, for mutations in the two mtDNA genes and flanking regions. In total, 43 different variants were identified, 31 of which were polymorphisms, one was a mutation (m.1555A-->G), two were known variants of controversial pathological nature (m.827A-->G and m.961delTinsC(n)) and nine were newly identified variants. The frequency of m.1555A-->G in this set of HL patients was 0.3%, which was lower than expected. To assess the putative causative nature of controversial or newly identified variants, the frequencies of these variants were determined in 400 Belgian control subjects, and their effect on the secondary structure and their conservation among different species was determined. Our data provide further support for a polymorphic nature of the controversial m.961delTinsC(n) variant. In addition, two of the newly identified variants, m.636A-->G in the 12SrRNA flanking tRNA(Phe) and m.990T-->C in 12SrRNA, may be new candidates for pathogenic HL variants. If the pathogenic nature of m.636A-->G can be confirmed, this would be the first NSHL mutation in tRNA(Phe).
authors.affiliation: Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Antwerp, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Konings
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.forename: Alain
authors.initials: A
authors.lastname: Goethals
authors.forename: Els
authors.initials: E
authors.lastname: Van Eyken
authors.forename: Ann
authors.initials: A
authors.lastname: Vandevelde
authors.forename: Jamila
authors.initials: J
authors.lastname: Ben Azza
authors.forename: Nils
authors.initials: N
authors.lastname: Peeters
authors.forename: Wim
authors.initials: W
authors.lastname: Wuyts
authors.forename: Hubert
authors.initials: H
authors.lastname: Smeets
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D004272:DNA, Mitochondrial / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics*; D012362:RNA, Transfer, Ser / Q000235:genetics*
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D012335:RNA, Ribosomal; D012362:RNA, Transfer, Ser; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26