Audiological Follow-Up of Children with the m.1555A&gt;G Mutation in Mitochondrial DNA

Häkli, Sanna; Luotonen, Mirja; Sorri, Martti; Majamaa, Kari

doi:10.1159/000342905

Cited by 10 publications

(4 citation statements)

References 60 publications

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“…Interestingly, the majority of those with homoplasmic status, comparable with our group, demonstrated early onset of hearing loss at between 1 and 5 years of age. Analogous results were presented by Hakli et al [ 23 [. Chen Chi Wu et al reported 30 individuals with hearing loss caused by the m.1555A>G mutation [ 9 ] and found early onset of hearing loss in 23 of them (in 8 individuals under 10 years of age, in the remaining 15 between 10 and 20 years of age).…”

Section: Discussionsupporting

confidence: 89%

Audio Profiles in Mitochondrial Deafness m.1555A>G and m.3243A>G Show Distinct Differences

et al. 2015

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BackgroundHearing loss is one of the most common symptoms of mitochondrial disorders. However, audiological phenotypes associated with different molecular defects in mtDNA are not yet well characterized.Material/MethodsA large cohort of 1499 nonconsanguineous patients aged 5–40 years with hearing loss of unknown etiology was screened for mutations in mtDNA. For further analysis, patients harboring m.1555A>G and m.3243A>G were selected.Hearing status of the patients was assessed by pure tone audiometry. Patterns of audiograms (hearing threshold levels at each examined frequency) were statistically compared among the carriers of the m.1555A>G and the m.3243A>G mutations.ResultsWe identified 20 patients positive for m.1555A>G mutation and 16 patients positive for m.3243A>G change. The frequency of the above transitions was calculated in our cohort as 1.33% and 1.06%, respectively. Seventeen affected family members carrying the mutations were included into the study.Typical shape of the audiograms in patients with m.1555A>G mutation presented a ski-slope pattern, whereas the audiometric curves among the m.3243A>G individuals had a pantonal shape (a flat curve) with slight downward sloping at the higher frequencies. The differences were statistically significant.The onset of hearing loss was noted earlier among m.1555A>G than m.3243A>G patients (12.5 and 26 years, respectively). Aminoglycoside administration was declared in both groups in 11 and 4 cases respectively, and caused abrupt hearing deterioration in all cases.ConclusionsA pattern of audiogram in patients with mitochondrial deafness may suggest a localization of mtDNA mutation. The pathogenesis of the audiometric differences needs further study.

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Section: Discussionsupporting

confidence: 89%

Audio Profiles in Mitochondrial Deafness m.1555A>G and m.3243A>G Show Distinct Differences

et al. 2015

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“…Her HI progressed to be severe by age 10.2 years and she received a cochlear implant at age 11.3 years. Her mother and five of her eight siblings had HI [ 23 ]. In this pedigree we were able to ascertain four children with HI, who harboured m.1555A > G and who had been born between the years 1993–2002 in Northern Finland.…”

Section: Resultsmentioning

confidence: 99%

Mutations in the two ribosomal RNA genes in mitochondrial DNA among Finnish children with hearing impairment

et al. 2015

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BackgroundMutations in the two MT-RNR genes in mitochondrial DNA can cause hearing impairment that presents with variable severity and age of onset. In order to study the prevalence of mutations in MT-RNR1 and MT-RNR2 genes among Finnish children, we studied a ten-year cohort of hearing impaired children born in Northern Finland.MethodsWe studied children, who had been born in Northern Finland in 1993–2002 and who had been ascertained to have hearing impairment by 31 December 2007. Samples from 103 children were sequenced in order to find mutations in the MT-RNR1 and MT-RNR2 genes.ResultsOne child harboured the pathogenic m.1555A > G mutation in MT-RNR1 suggesting a frequency of 4.4/100,000 in the Finnish paediatric population. In addition, eight rare variants and 13 polymorphisms were found in MT-RNR1 and MT-RNR2 genes. Five of the rare variants were deemed to be haplogroup-specific polymorphisms rather than putative pathogenic mutations, while the remaining three variants have been reported in various haplogroups. Among them m.990 T > C occurs at a conserved site.ConclusionsThe presence of m.990 T > C variant in various haplogroups and the rather high degree of conservation at this site suggest that this transition is a pathogenic rather than homoplasic neutral variant. Identification of further patients with m.990 T > C and segregation analysis in their families should help in determining the pathogenic potential of this variant.

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“…However, family studies of m.1555A>G carriers indicate a very high penetrance of permanent hearing loss if aminoglycosides are given [ 5 ], and a recently published follow up study including 19 Finish m.1555A>G carriers reported that all children passed the newborn hearing screening, but 10 of 19 developed permanent hearing loss at a median age of 3.7 years [ 15 ]. Therefore, our current data might considerably underestimate the long term effect of the aminoglycoside use in preterm infants carrying m.1555A>G.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants

et al. 2014

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BackgroundThe mitochondrial m.1555A>G mutation is associated with a high rate of permanent hearing loss, if aminoglycosides are given. Preterm infants have an increased risk of permanent hearing loss and are frequently treated with aminoglycoside antibiotics.MethodsWe genotyped preterm infants with a birth weight below 1500 grams who were prospectively enrolled in a large cohort study for the m.1555A>G mutation. Treatment with aminoglycoside antibiotics in combination with mitochondrial m.1555A>G mutation was tested as a predictor for failed hearing screening at discharge in a multivariate logistic regression analysis.Results7056 infants were genotyped and analysed. Low birth weight was the most significant predictor of failed hearing screening (p = 7.3 × 10-10). 12 infants (0.2%) had the m.1555A>G-mutation. In a multivariable logistic regression analysis, the combination of aminoglycoside treatment with m.1555A>G-carrier status was associated with failed hearing screening (p = 0.0058). However, only 3 out of 10 preterm m.1555A>G-carriers who were exposed to aminoglycosides failed hearing screening. The m.1555A>G-mutation was detected in all mothers of m.1555A>G-positive children, but in none of 2993 maternal DNA-samples of m.1555A>G-negative infants.ConclusionAntenatal screening for the m.1555A>G mutation by maternal genotyping of pregnant women with preterm labour might be a reasonable approach to identify infants who are at increased risk for permanent hearing loss. Additional studies are needed to estimate the relevance of cofactors like aminoglycoside plasma levels and birth weight and the amount of preterm m.1555A>G-carriers with permanent hearing loss.

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Audiological Follow-Up of Children with the m.1555A>G Mutation in Mitochondrial DNA

Cited by 10 publications

References 60 publications

Audio Profiles in Mitochondrial Deafness m.1555A>G and m.3243A>G Show Distinct Differences

Audio Profiles in Mitochondrial Deafness m.1555A>G and m.3243A>G Show Distinct Differences

Mutations in the two ribosomal RNA genes in mitochondrial DNA among Finnish children with hearing impairment

Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants

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