A maternal hereditary deafness pedigree of the A1555G mitochondrial mutation, causing aminoglycoside ototoxicity predisposition

Yh, Bai; Cc, Ren; Xr, Gong; Lp, Meng

doi:10.1017/s0022215107001648

Cited by 7 publications

(8 citation statements)

References 16 publications

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“…These mitochondrial variants produce variable clinical severity with age of onset ranging from congenital to adulthood (Guan, ). Pathogenic alleles in the MT‐RNR1 gene can cause maternally inherited, nonsyndromic hearing loss which is induced or aggravated by ototoxic aminoglycosides such as gentamicin, kanamycin and streptomycin (Fischel‐Ghodsian et al., ; Gardner et al., ; Usami et al., ; Estivill et al., ; Li et al., ; Bai et al., ; Lu et al., 2010). However, in the absence of aminoglycoside antibiotics, the variants in the MT‐RNR1 gene produce the same phenotypes (Prezant et al., ; Shoffner et al., ; Bacino et al., ; Matthijs et al., ; Pandya et al., ; Estivill et al., ; Matsunaga et al., ; Liu et al., ; Zhu et al., ; Shen et al., ).…”

Section: Introductionmentioning

confidence: 99%

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

Subathra

Ramesh

Selvakumari

et al. 2016

Annals of Human Genetics

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Mitochondria play a critical role in the generation of metabolic energy in the form of ATP. Tissues and organs that are highly dependent on aerobic metabolism are involved in mitochondrial disorders including nonsyndromic hearing loss (NSHL). Seven pathogenic variants leading to NSHL have so far been reported on two mitochondrial genes: MT-RNR1 encoding 12SrRNA and MT-TS1 encoding tRNA for Ser((UCN)) . We screened 729 prelingual NSHL subjects to determine the prevalence of MT-RNR1 variants at position m.961, m.1555A>G and m.1494C>T, and MT-TS1 m.7445A>G, m.7472insC m.7510T>C and m.7511T>C variants. Mitochondrial pathogenic variants were found in eight probands (1.1%). Five of them were found to have the m.1555A>G variant, two others had m.7472insC and one proband had m.7444G>A. The extended relatives of these probands showed variable degrees of hearing loss and age at onset. This study shows that mitochondrial pathogenic alleles contribute to about 1% prelingual hearing loss. This study will henceforth provide the reference for the prevalence of mitochondrial pathogenic alleles in the South Indian population, which to date has not been estimated. The m.1555A>G variant is a primary predisposing genetic factor for the development of hearing loss. Our study strongly suggests that mitochondrial genotyping should be considered for all hearing impaired individuals and particularly in families where transmission is compatible with maternal inheritance, after ruling out the most common variants.

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Section: Introductionmentioning

confidence: 99%

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

Subathra

Ramesh

Selvakumari

et al. 2016

Annals of Human Genetics

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“…In addition, the mutation m.1555A>G has been associated with aminoglycoside-induced and nonsyndromic hearing loss. Different familial studies revealed that the m.1555A>G mutation carriers are susceptible to hearing loss after treatment with aminoglycosides even at low doses (Gardner et al, 1997;Fischel-Ghodsian et al, 1997;Usami et al, 1997;Estivill et al, 1998;Bai et al 2008). However, in the absence of aminoglycoside exposure the same mutation produces a clinical phenotype that varies considerably among family members and ranges from (i) severe congenital hearing loss, (ii) to moderate progressive hearing loss of later onset, (iii) to completely normal hearing (Prezant et al, 1993;Shoffner et al, 1994;Matthijs et al, 1996;Pandya et al, 1997;Estivill et al, 1998;Matsunaga et al, 2005;Liu et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Complete Mitochondrial Genome Analysis and Clinical Documentation of a Five-Generational Indian Family with Mitochondrial 1555A>G Mutation and Postlingual Hearing Loss

Subathra

Selvakumari

Ramesh

et al. 2014

Annals of Human Genetics

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SummaryHearing loss is the most common sensory disorder and is genetically heterogeneous. Apart from nuclear gene mutations, a number of inherited mitochondrial mutations have also been implicated. The m.1555A>G mutation in the mitochondrial MT-RNR1 gene is reported as the most common mutation causing nonsyndromic hearing loss in various ethnic populations. We report here for the first time the clinical, genetic and molecular characterisation of a single large five-generational Tamil-speaking South Indian family with maternally inherited nonsyndromic postlingual hearing loss. Molecular analysis led to identification of m.1555A>G in 28 maternal relatives with variable degree of phenotypic expression. The penetrance of hearing loss among the maternal relatives in this family was 55%. Sequence analysis of the complete mitochondrial genome in 36 members of this pedigree identified 25 known variants and one novel variant co-transmitted along with m.1555A>G mutation. The mtDNA haplotype analysis revealed that the maternal relatives carry the R * T 2 haplotype similar to Europeans and South Asians. Sequencing of the coding exon of GJB2 nuclear gene did not show any pathogenic mutations. The results suggest that other nuclear or environmental modifying factors could have played a role in the differential expression of mutation m.1555A>G in postlingual hearing loss in this family.

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“…Forty-two articles[ 3 6 7 9 10 11 12 13 16 17 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 ] (the others are as shown in Figure 2 ) addressed the prevalence/incidence of MT-RNR1 mutation in the populations with SNHL for which a range of 0% in Brazilian[ 30 ] and Argentine[ 32 ] subjects to 100% in 3 Spanish families[ 31 ] with aminoglycoside-induced hearing loss were presented. The modal prevalence was 3.2% and only A1555G and/or C1494T variants were assessed.…”

Section: Methodsmentioning

confidence: 99%

“…Three papers documented ototoxicity in patients with no observed MT-RNR1 mutations[ 9 21 24 ] while two papers had no hearing impairment among patients with the mutation with or without the gentamicin exposure. [ 26 33 ] Eight papers[ 7 17 22 26 29 35 36 37 ] recorded a wide phenotypic variance of hearing impairment, age-of-onset and audiometric configurations in patients with the mutation and hearing impairment.…”

Section: Methodsmentioning

confidence: 99%

A meta-analysis and systematic review of the prevalence of mitochondrially encoded 12S RNA in the general population: Is there a role for screening neonates requiring aminoglycosides?

Ibekwe¹,

Bhimrao²,

Westerberg³

et al. 2015

Afr J Paediatr Surg

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Background:This was a meta-analysis and systematic review to determine the global prevalence of the mitochondrially encoded 12S RNA (MT-RNR1) genetic mutation in order to assess the need for neonatal screening prior to aminoglycoside therapy.Materials and Methods:A comprehensive search of MEDLINE, EMBASE, Ovid, Database of Abstracts of Reviews of Effect, Cochrane Library, Clinical Evidence and Cochrane Central Register of Trials was performed including cross-referencing independently by 2 assessors. Selections were restricted to human studies in English. Meta-analysis was done with MetaXL 2013.Results:Forty-five papers out of 295 met the criteria. Pooled prevalence in the general population for MT-RNR1 gene mutations (A1555G, C1494T, A7445G) was 2% (1–4%) at 99%.Conclusion:Routine screening for MT-RNR1 mutations in the general population prior to treatment with aminoglycosides appear desirable but poorly supported by the weak level of evidence available in the literature. Routine screening in high-risk (Chinese and Spanish) populations appear justified.

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A maternal hereditary deafness pedigree of the A1555G mitochondrial mutation, causing aminoglycoside ototoxicity predisposition

Abstract: We confirmed that the A1555G mutation is a 'hot spot' associated with non-syndromic, inherited hearing loss. This mutation may play a vital role in the pathogenesis of hearing impairment, and can result in various grades of deafness.

Cited by 7 publications

References 16 publications

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals

Complete Mitochondrial Genome Analysis and Clinical Documentation of a Five-Generational Indian Family with Mitochondrial 1555A>G Mutation and Postlingual Hearing Loss

A meta-analysis and systematic review of the prevalence of mitochondrially encoded 12S RNA in the general population: Is there a role for screening neonates requiring aminoglycosides?

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