Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.
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.
Prezant
T R
TR
Ahmanson Department of Pediatrics Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, California.
Agapian
J V
JV
Bohlman
M C
MC
Bu
X
X
Oztas
S
S
Qiu
W Q
WQ
Arnos
K S
KS
Cortopassi
G A
GA
Jaber
L
L
Rotter
J I
JI
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*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D012313:RNA