Second family with hearing impairment linked to 19q13 and refined DFNA4 localisation

Mirghomizadeh, Farhad; Bardtke, Bettina; Devoto, Marcella; Pfister, Markus; Oeken, Jens; König, Elke; Vitale, Emilia; Riccio, Antonio; Rienzo, Assunta De; Zenner, H. P.; Blin, Nikolaus

doi:10.1038/sj.ejhg.5200769

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…MYH14 encodes one of the heavy chains of the class II nonmuscle myosins (i.e., heavy chain 14). This gene resides within the DFNA4 locus, 27,28 suggesting the possible contribution of this gene to deafness, even though the heterogeneity of this locus was reported subsequently. 29,30 By evaluating four families with cosegregating moderate SNHL and a MYH14 mutation, Donaudy et al 31 reported a substantial contribution of MYH14 mutations to hereditary SNHL.…”

Section: Genetics In Medicine | Volume 17 | Number 11 | November 2015mentioning

confidence: 95%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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Purpose: This study was designed to delineate genetic contributions, if any, to sporadic forms of mild to moderate sensorineural hearing loss (SNHL) not related to GJB2 mutations (DFNB1) in a pediatric population. Methods:We recruited 11 non-DFNB1 simplex cases of mild to moderate SNHL in children. We applied whole-exome sequencing to all 11 probands. We used a filtering strategy assuming that de novo variants of known autosomal dominant (AD) deafness genes, biallelic mutations in autosomal recessive (AR) genes, monoallelic mutations in X chromosome genes for males, and digenic inheritance could be associated. Candidate variants first were prioritized with allele frequency in public databases and confirmed by a phase or a segregation test in each family. Additional information from the literature or public databases was used to identify strong candidate variants.Results: Strong candidate variants were detected in 5 of 11 probands (45.4%). A diverse mode of inheritance implicated the sporadic occurrence of the phenotype. AR mutations in OTOGL and SERPINB6 and digenic inheritance involving two deafness genes, GPR98 and PDZ7, were detected. A de novo AD mutation also was detected in TECTA and MYH14. No syndromic feature was detected in individuals with GPR98/PDZ7 or MYH14 variants in our cohort at this moment. Conclusion:Mild to moderate pediatric SNHL, even if sporadic, features a strong genetic etiology and can manifest via diverse modes of inheritance. In addition, a multidisciplinary approach should be used for a correct diagnosis. Genet Med advance online publication 26 February 2015

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Section: Genetics In Medicine | Volume 17 | Number 11 | November 2015mentioning

confidence: 95%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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“…MYH14 can lead to two different conditions: DFNA4 with progressive non syndromic hearing loss starting in the first or second decade of life and leading to severe to profound hearing loss in the fourth decade of life (Firstly described by Mirghomizadeh et al, ); or to IPN associated with myopathy, hoarseness, and hearing loss (Choi et al, ). This phenotype is only reported in one article.…”

Section: Discussionmentioning

confidence: 99%

“…MYH14 c ould nevertheless be also responsible for IPN. Actually, only one case has been reported with IPN and hearing loss (Choi et al, ), and two articles have been published about hearing loss with the same pathogenic variants (Chen et al, ; Mirghomizadeh et al, ).We can wonder whether a founder effect exists, or if a pathogenic variant in a HL gene close to MYH14 exists.…”

Section: Discussionmentioning

confidence: 99%

Hearing loss in inherited peripheral neuropathies: Molecular diagnosis by NGS in a French series

Lerat

Magdelaine

Roux

et al. 2019

Molec Gen & Gen Med

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Background The most common inherited peripheral neuropathy is Charcot‐Marie‐Tooth disease (CMT), with a prevalence of 1/2500. Other symptoms can be associated to the condition, such as hearing loss. Currently, no global hearing impairment assessment has been determined, and the physiopathology is not well known. Methods The aim of the study was to analyze among a French series of 3,412 patients with inherited peripheral neuropathy (IPN), the ones who also suffer from hearing loss, to establish phenotype‐genotype correlations. An NGS strategy for IPN one side and nonsyndromic hearing loss (NSHL) on the other side, were performed. Results Hearing loss (HL) was present in only 44 patients (1.30%). The clinical data of 27 patients were usable. Demyelinating neuropathy was diagnosed in 15 cases and axonal neuropathy in 12 cases. HL varied from mild to profound. Five cases of auditory neuropathy were noticed. Diagnosis was made for 60% of these patients. Seven novel pathogenic variants were discovered in five different genes: PRPS1; MPZ; SH3TC2; NEFL; and ABHD12. Two patients with PMP22 variant, had also an additional variant in COCH and MYH14 respectively. No pathogenic variant was found at the DFNB1 locus. Genotype‐phenotype correlations do exist, especially with SH3TC2, PRPS1, ABHD12, NEFL, and TRPV4. Conclusion Involvement of PMP22 is not enough to explain hearing loss in patients suffering from IPN. HL can be due to cochlear impairment and/or auditory nerve dysfunction. HL is certainly underdiagnosed, and should be evaluated in every patient suffering from IPN.

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“…TWIK‐2 maps within this interval, as illustrated in Figure 1. Two additional families, an unrelated U.S. family (family 1030) and a German family (Leipzig 9; Mirghomizadeh et al, 2002) with autosomal dominant hereditary hearing loss have also been mapped to chromosome 19. The mapped loci of these two families partially overlaps with the interval delimited by markers D19S414 and D19S246 at its proximal and distal ends (Fig.…”

Section: Resultsmentioning

confidence: 99%

Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4

Mhatre¹,

Jiang²,

Chen³

et al. 2003

J of Neuroscience Research

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KCNK6 encodes a tandem pore domain potassium channel, TWIK-2, that maps to chromosome 19. Both STS and linkage maps established KCNK6 as a positional candidate gene for DFNA4, a form of autosomal dominant nonsyndromic hereditary hearing loss. Identification and characterization of Kcnk6 expression within the mammalian cochlea established the gene as a functional candidate for DFNA4. Identification of Twik-2 expression in the mouse cochlea was initially established via RT-PCR assay of cochlear RNA. Subsequent immunoblot analysis of cochlear homogenate yielded a distinct 35-kDa band corresponding to the calculated molecular weight of the mouse Twik-2. Immunohistochemical studies localized Twik-2 expression in the cochlea predominantly within the stria vascularis. This vascular tissue borders the cochlear duct and is a critical regulator of potassium concentration in the endolymph. Genomic structure of TWIK-2 was subsequently determined and shown to consist of three coding exons with splice acceptor and donor sites in accordance with the consensus GT-AG rule. Two separate DFNA4 families were screened for KCNK6 sequence alterations. No mutations were found, thus excluding TWIK-2 as the DFNA4 candidate disease gene. Nevertheless, expression of Twik-2 within the stria vascularis suggests a potential role for this protein as one of the terminal components of the potassium ion-recycling pathway that contributes toward its reabsorption into the endolymph.

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Second family with hearing impairment linked to 19q13 and refined DFNA4 localisation

Cited by 11 publications

References 17 publications

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Hearing loss in inherited peripheral neuropathies: Molecular diagnosis by NGS in a French series

Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4

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