title: Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss.
abstract: Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed mutational screening of entire 12S rRNA gene in 250 unrelated patients with non-syndromic and aminoglycoside-induced hearing loss. Twenty-one different homoplasmic sequence variants were identified, including eight common polymorphisms, one deafness-associated mutation m.1555 A>G and three putatively pathogenic variants: m.669 T>C, m.827 A>G, m.961 delT+C(n)ins. The incidence of m.1555 A>G was estimated for 3.6% (9/250); however, where aminoglycoside exposure was taken as a risk factor, the frequency was 5.5% (7/128). Substitution m.669 T>C was identified only in patients with hearing impairment and episode of aminoglycoside exposure, which may suggest that such additional risk factors must appear to induce clinical phenotype. Moreover, two 12S rRNA sequence variants: m.988 G>A and m.1453 A>G, localized at conserved sites and affected RNA secondary structure, may be new candidates for non-syndromic and aminoglycoside-induced hearing loss associated mutations.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland. marydz@man.poznan.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.forename: Maciej
authors.initials: M
authors.lastname: Wróbel
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pollak
authors.forename: Wojciec
authors.initials: W
authors.lastname: Gawecki
authors.forename: Damian
authors.initials: D
authors.lastname: Brauze
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kostrzewska-Poczekaj
authors.forename: Irena
authors.initials: I
authors.lastname: Wojsyk-Banaszak
authors.forename: Urszula
authors.initials: U
authors.lastname: Lechowicz
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Mueller-Malesińska
authors.forename: Monika
authors.initials: M
authors.lastname: Ołdak
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.forename: Henryk
authors.initials: H
authors.lastname: Skarzyński
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szyfter
mesh_terms: D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D050259:Genes, Mitochondrial; D005820:Genetic Testing; D034381:Hearing Loss / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011044:Poland; D011110:Polymorphism, Genetic; D012335:RNA, Ribosomal / Q000235:genetics*; D044465:White People; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S