Genetic susceptibility to aminoglycoside ototoxicity: How many are at risk?

Abstract

Purpose: To assess the occurrence of two mutations associated with susceptibility to aminoglycoside ototoxicity.Methods: Genetic analysis of anonymized, residual diagnostic specimens. Results: One occurrence of the A1555G mutation and seven occurrences of the 961delT ϩ C(n) nucleotide change were found. Two previously unreported sequence changes, T961G and 956 -960insC, were also found in six and five specimens, respectively. Conclusions: Genetic susceptibility to aminoglycoside ototoxicity may be more common than previously suspected.Further study of the 961delT ϩ C(n) mutation is recommended to confirm its role in aminoglycoside ototoxicity and assess penetrance and variability with and without exposure to aminoglycoside antibiotics. Genet Med 2002:4(5):336 -345.

Rastreamento da mutação mitocondrial A1555G em pacientes com deficiência auditiva sensorioneural

“…The first of these sampled umbilical cord blood of 1,773 neonates, of which only one carried the mutation. 27 The second screened 25 neonates that had altered otoacoustic emissions tests, among which the mutation was not found. 28 Screening of 300 neonates in Argentina and in 712 normal-hearing subjects did not detect the A1555G mutation.…”

“…12 Although the number of cases in both groups was different from the number in some published studies, and although the mutation was not found in both groups (HLG and control groups), we were able to confirm the results of studies that also did not find the mutation in non-Asian or Arab ethnic groups. [24][25][26][27][28][29] There is a single study in Brazil reporting the findings of five families with hearing loss cases in which the prevalence of the mutation was 2% (4 cases). Only one of these positive cases was associated with an assumed aminoglycoside exposure; no mutation was found in the control group composed by black, white or Asian (Japanese or Chinese) ethnic groups.…”

New Variants of European Brown Hare Syndrome Virus Strains in Free-Ranging European Brown Hares (Lepus Europaeus) From Slovakia

“…To determine whether an inherited susceptibility (Tang et al, 2002) exists among the investigated hares, we also examined the matrilinear haplotypes of all tissue samples (n585). Fifteen different haplotypes were found, but there was neither a significant correlation between haplotype and development of antibodies nor between haplotype and harboring of EBHSV infection.…”

Mitochondrial rRNA and tRNA and hearing function

“…Mutations in this gene cause aminoglycoside-induced and nonsyndromic SNHL, which may be due to the A1555G [23][24][25][26][27], C1494T [28], T1095C [34][35][36][37], A827G [40,41], and 961 mutations [30][31][32][33]. No deafness-associated mutations in the mitochondrial 16S rRNA gene have been detected.…”

“…By now, several mutations including A1555G [23][24][25][26][27], C1494T [28], T1095C [34][35][36][37], A827G [40,41], and 961 mutation [30][31][32][33] in the mitochondrial 12S rRNA gene have been found to be associated with nonsyndromic hearing loss. Surprisingly, all of these mutations are sensitive to aminoglycosides as indicated by extensive clinical observations and functional studies [5,41,68].…”