Audiologic presentation of enlargement of the vestibular aqueduct according to the <scp>SLC</scp>26<scp>A</scp>4 genotypes

Rah, Yoon Chan; Kim, Ah R.; Koo, Ja Won; Lee, Jun H.; Oh, Seung Ha; Choi, Byung Yoon

doi:10.1002/lary.25079

Cited by 43 publications

(29 citation statements)

References 19 publications

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“…The reported percentage of biallelic SLC26A4 mutations in EVA cohorts range from 8% to 84%, suggesting a multifactorial diversity within each ethnic population. It probably also reflects different strategies of ascertaining patients and the use of genetic testing.…”

Section: Discussionmentioning

confidence: 99%

Association of SLC26A4 mutations, morphology, and hearing in pendred syndrome and NSEVA

Mey¹,

Muhamad

Tranebjærg

et al. 2019

The Laryngoscope

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Objective: To investigate the relations of monoallelic (M1), biallelic (M2), or the absence of mutations (M0) in SLC26A4 to inner ear morphology and hearing levels in individuals with Pendred syndrome (PS) or nonsyndromic enlarged vestibular aqueduct (NSEVA) associated with hearing loss.Methods: In a cohort of 139 PS/NSEVA individuals, 115 persons from 95 unrelated families had full genetic sequencing of SLC26A4, and 113 had retrievable images for re-assessment of inner ear morphology. The association between the number of mutant alleles in SLC26A4, inner ear morphology (including endolymphatic sac size and protein content on magnetic resonance imaging), and hearing level (pure tone average) was explored.Results: Biallelic SLC26A4 mutations (M2) occurred in three-quarters of the cohort and was invariably associated with poor hearing; in 87%, it was associated with incomplete partition type II of the cochlea as well as enlarged endolymphatic sac and vestibular aqueduct. M1 or M0 individuals exhibited a greater variability in inner ear morphology. Endolymphatic sac size and presence of "high-protein" sac contents were significantly higher in M2 individuals compared to M1 and M0 individuals.Conclusion: The number of SLC26A4 mutations is associated with severity and variability of inner ear morphology and hearing level in individuals with PS or NSEVA. M2 individuals have poorer hearing and present largely incomplete partition type II of the cochleas with enlarged endolymphatic sacs, whereas individuals with M1 and no detectable SLC26A4 mutations have less severe hearing loss and more diverse inner ear morphology.

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Section: Discussionmentioning

confidence: 99%

Association of SLC26A4 mutations, morphology, and hearing in pendred syndrome and NSEVA

Mey¹,

Muhamad

Tranebjærg

et al. 2019

The Laryngoscope

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“…In general, genes and variants with autosomal recessive inheritance cause congenital or early onset (prelingual) deafness, whereas genes with autosomal dominant inheritance lead to progressive hearing loss often with delayed onset. However, about one-half of patients with bilateral and about 10 % with unilateral EVA harbor biallelic SLC26A4 mutations associated with autosomal recessive nonsyndromic deafness or Pendred syndrome (14,15). These patients may suffer from sudden hearing loss even after minor head trauma (16).…”

Section: Discussionmentioning

confidence: 99%

Hereditary bilateral sudden sensorineural hearing loss

Varga¹,

Jovankovičová²,

Hučková³

et al. 2019

BLL

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The aim of our study is to demonstrate a causal link between two distinct diagnoses, the hereditary hearing loss, and the sudden sensorineural hearing loss. BACKGROUND: Sudden sensorineural hearing loss is an emergency condition in otolaryngology and a rare diagnosis in childhood. Most often it only affects one ear and its cause remains unknown. METHODS: We present a clinical study of a 10-year-old female patient presenting with bilateral sudden sensorineural hearing loss analyzed by Sanger sequencing of the GJB2 gene. RESULTS: The subject was referred to the hospital for bilateral sudden hearing loss which developed 3 days before the admission. Audiometric testing confi rmed bilateral asymmetric sensorineural hearing loss. All routine diagnostic procedures including MRI and CT imaging showed normal results. She was treated with intravenous and intratympanic corticosteroids followed by hyperbaric oxygen therapy with partial hearing recovery in one ear. DNA analysis of the GJB2 gene identifi ed biallelic c.35delG deletion. The subject had no other affected family members and her auditory development to that time was normal. CONCLUSION: Our fi nding extends the knowledge on phenotype variability in GJB2 variants. We suggest considering genetic testing in pediatric cases of bilateral sudden sensorineural hearing loss (Tab. 1, Fig. 4, Ref. 24).

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“…In several studies, the authors did not identify any phenotypic differences among patients with different SLC26A4 variants [26,34]. However, it has been recently reported that some variants might lead to progression of hearing loss [35,36], and some SLC26A4 genotypes might be associated with a normal thyroid phenotype and less severe hearing loss [37].…”

Section: Discussionmentioning

confidence: 96%

Toward the pathogenicity of the SLC26A4 p.C565Y variant using a genetically driven mouse model

Yang

et al. 2020

Preprint

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Recessive variants of the SLC26A4 gene are a common cause of hearing impairment worldwide. In the past, cell lines and transgenic mice have been widely used to investigate the pathogenicity associated with the SLC26A4 variants. However, discrepancies in the pathogenicity between humans and cell lines or transgenic mice have been documented for some of the SLC26A4 variants. For instance, the p.C565Y variant, which has been reported to be pathogenic in humans, did not exhibit functional pathogenic consequences in cell lines. To address the pathogenicity of p.C565Y, we used a genotype-based approach in which we generated knock-in mice heterozygous (Slc26a4 +/C565Y ), homozygous (Slc26a4 C565Y/C565Y ), and compound heterozygous (Slc26a4 919-2A>G/C565Y ) for this variant. Subsequent phenotypic characterization revealed that mice segregating these genotypes demonstrated normal auditory and vestibular functions and normal inner ear morphology and expression of pendrin. These findings indicate that the p.C565Y variant is non-pathogenic for mice and that a single p.C565Y allele is sufficient to maintain normal inner ear physiology in mice. Our results highlight the differences in the pathogenicity associated with certain SLC26A4 variants between transgenic mice and humans, which should be taken into consideration while interpreting the results of animal studies for SLC26A4-related deafness.

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Audiologic presentation of enlargement of the vestibular aqueduct according to the SLC26A4 genotypes

Abstract: NA.

Cited by 43 publications

References 19 publications

Association of SLC26A4 mutations, morphology, and hearing in pendred syndrome and NSEVA

Association of SLC26A4 mutations, morphology, and hearing in pendred syndrome and NSEVA

Hereditary bilateral sudden sensorineural hearing loss

Toward the pathogenicity of the SLC26A4 p.C565Y variant using a genetically driven mouse model

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