Screening of the general Polish population for deafness-associated mutations in mitochondrial 12S rRNA and tRNA Ser(UCN) genes.
Mutations in mitochondrial DNA are associated potentially with nonsyndromic and aminoglycoside-induced hearing loss. Several nucleotide changes associated with hearing impairment were described; however, a variable frequency of deafness-associated mutations in different populations has been observed. The aim of the present study was to determine the frequency of pathological mutations in mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes in a group of 500 individuals representative of the general population of Poland. Mutational screening of 12S rRNA revealed the presence of three deafness-associated mutations, A827G, T961C, and A1555G, and one potentially pathogenic substitution, T669C. The carrier frequency of pathological mutations was estimated to be 1.2% (6/500) in the general Polish population. A deafness-associated G7444A mutation in the precursor of tRNA(Ser(UCN)) gene was identified in 8/500 (1.6%) unrelated blood donors. Seven nucleotide changes identified in 12S rRNA (G709A, G750A, G930A, T1243C, T1420C, and G1438A) and tRNA(Ser(UCN)) (C7476T), based on a frequency exceeding 1.0%, were considered as polymorphisms of 12S rRNA and tRNA(Ser(UCN)) in the studied population. Mitochondrial 12S rRNA gene seems to be the hot spot for deafness-associated mutations in the Polish population. The relatively high carrier frequency of tRNA(Ser(UCN)) G7444A (1/62) suggests that this substitution might be a nonpathogenic polymorphism in the Polish population.
Rydzanicz
Małgorzata
M
Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland. marydz@man.poznan.pl
Wróbel
Maciej
M
Cywińska
Karolina
K
Froehlich
Dominika
D
Gawecki
Wojciech
W
Szyfter
Witold
W
Szyfter
Krzysztof
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing / Q000379:methods*; D005843:Geography; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011044:Poland; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D044382:Population Groups / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics*; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics*; D017423:Sequence Analysis, RNA; D044465:White People / Q000235:genetics; D055815:Young Adult
D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; D012346:RNA, Transfer, Amino Acyl; C075526:RNA, ribosomal, 12S