Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss.
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.
Rydzanicz
Małgorzata
M
Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland. marydz@man.poznan.pl
Wróbel
Maciej
M
Pollak
Agnieszka
A
Gawecki
Wojciec
W
Brauze
Damian
D
Kostrzewska-Poczekaj
Magdalena
M
Wojsyk-Banaszak
Irena
I
Lechowicz
Urszula
U
Mueller-Malesińska
Małgorzata
M
Ołdak
Monika
M
Płoski
Rafał
R
Skarzyński
Henryk
H
Szyfter
Krzysztof
K
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
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S