title: Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.
abstract: Maternally transmitted non-syndromic deafness was described recently both in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree. Because of the known action of aminoglycosides on bacterial ribosomes, we analysed the sequence of the mitochondrial rRNA genes of three unrelated patients with familial aminoglycoside-induced deafness. We also sequenced the complete mitochondrial genome of the Arab-Israeli pedigree. All four families shared a nucleotide 1555 A to G substitution in the 12S rRNA gene, a site implicated in aminoglycoside activity. Our study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non-syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic-induced ototoxicity.
authors.affiliation: Ahmanson Department of Pediatrics Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: T R
authors.initials: TR
authors.lastname: Prezant
authors.forename: J V
authors.initials: JV
authors.lastname: Agapian
authors.forename: M C
authors.initials: MC
authors.lastname: Bohlman
authors.forename: X
authors.initials: X
authors.lastname: Bu
authors.forename: S
authors.initials: S
authors.lastname: Oztas
authors.forename: W Q
authors.initials: WQ
authors.lastname: Qiu
authors.forename: K S
authors.initials: KS
authors.lastname: Arnos
authors.forename: G A
authors.initials: GA
authors.lastname: Cortopassi
authors.forename: L
authors.initials: L
authors.lastname: Jaber
authors.forename: J I
authors.initials: JI
authors.lastname: Rotter
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D001483:Base Sequence; D003638:Deafness / Q000139:chemically induced / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006801:Humans; D007557:Israel; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D012313:RNA