Non-syndromic hereditary sensorineural hearing loss: review of the genes involved

Stelma, F; Bhutta, Mahmood F.

doi:10.1017/s0022215113003265

Cited by 29 publications

(33 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, over 100 genes have been identified for non‐syndromic hearing loss (NSHL) (http://hereditaryhearingloss.org). These genes are involved in a broad spectrum of molecular and cellular mechanisms, such as hair bundle morphogenesis, planar cell polarity, ion homeostasis or serve as transcription factors, which are essential for the normal development and maintenance of auditory processing . Research into the identification and function of deafness‐associated genes has been the most efficient way to broaden our knowledge of auditory physiology.…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing identified a second pathogenic variant in HOMER2 for autosomal dominant non‐syndromic deafness

Wang

et al. 2018

Clinical Genetics

View full text Add to dashboard Cite

Hearing loss is one of the most common sensory disorders worldwide, and about half of all occurrences are attributable to genetic factors. Here, we have identified a novel pathogenic variant in HOMER2 in a Chinese family with autosomal dominant, non-syndromic hearing loss. This is the second family reported globally with hearing loss caused by a variant in HOMER2. The pathogenic variant c.840_841insC in HOMER2 (NM_199330), segregating with the hearing-loss phenotype in the family, leads to a premature stop codon producing a truncated protein. The coiled-coil domain in the C-terminal of HOMER2 protein is essential for protein multimerization and HOMER2-CDC42 interaction. We compared the phenotypes in the two families and found that hearing impairment in this Chinese family was more severe. Furthermore, we found that the ability of this insertion mutant type HOMER2 (HOMER2 ) to multimerize decreased more significantly than wild-type HOMER2 (HOMER2 ) and the reported c.554G>C (NM_004839) mutant HOMER2. HOMER2 protein tended to be distributed in a diffuse manner, whereas HOMER2 and the reported mutant HOMER2 tended to cluster together. Our research provides a validating second family for variants in HOMER2 causing non-syndromic sensorineural hearing loss. HOMER2 homo-/hetero-multimerization might be the first step in exerting its normal function.

show abstract

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing identified a second pathogenic variant in HOMER2 for autosomal dominant non‐syndromic deafness

Wang

et al. 2018

Clinical Genetics

View full text Add to dashboard Cite

show abstract

“…The phenotype of DFNA9 patients due to mutations in COCH gene varies and correlates with the location of the mutation in cochlin [22, 23]. Families carrying mutations in the LCCL domain are more likely to have hearing loss and self-reported vestibular dysfunction, whereas those carrying mutations in the vWFA domain present with severe hearing loss without complaints of vestibular symptoms [20].…”

Section: Introductionmentioning

confidence: 99%

Different Phenotypes of the Two Chinese Probands with the Same c.889G>A (p.C162Y) Mutation in COCH Gene Verify Different Mechanisms Underlying Autosomal Dominant Nonsyndromic Deafness 9

Wang

Fei

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

ObjectivesBy analyzing the different phenotypes of two Chinese DFNA9 families with the same mutation located in the intervening region between the LCCL and vWFA domains of cochlin and testing the functional changes in the mutant cochlin, we investigated the different pathogeneses for mutations in LCCL and vWFA domains.MethodsTargeted next-generation sequencing for deafness-related genes was used to identify the mutation in the proband in family #208. The probands of family #208 and family #32 with the same p.C162Y mutation were followed for more than 3 years to evaluate the progression of hearing loss and vestibular dysfunction using pure-tone audiometry, caloric testing, electrocochleogram, vestibular-evoked myogenic potential, and video head-impulse test. The disruption of normal cleavage to produce secreted LCCL domain fragments and the tendency to form aggregations of mutant cochlins were tested by in vitro cell experiments.ResultsThe two families showed different clinical symptoms. Family #32 was identified as having early-onset, progressive sensorineural hearing loss, similar to the symptoms in DFNA9 patients with cochlin mutations in the vWFA domain. The proband of family #208 endured late-onset recurrent paroxysmal vertigo attacks and progressively deteriorating hearing, similar to symptoms in those with cochlin mutations in the LCCL domain. We therefore suggest that the disrupted cleavage of the LCCL domain fragment is likely to cause vestibular dysfunction, and aggregation of mutant cochlin caused by mutations in the vWFA domain is responsible for early-onset hearing loss. The p.C162Y mutation causes either disruption of LCCL domain fragment cleavage or aggregation of mutant cochlin, resulting in the different phenotypes in the two families.ConclusionThis study demonstrates that DFNA9 families with the same genotype may have significantly different phenotypes. The mutation site in cochlin is related to the pathological mechanism underlying the different phenotypes.

show abstract

“…Depending on the studied population, 20–50% of all recessive nonsyndromic SNHL cases can be attributed to a mutation in GJB2 (Hilgert et al, 2009a; Linden Phillips et al, 2013). For a comprehensive overview of other affected genes, we refer to recent reviews (Hilgert et al, 2009b; Angeli et al, 2012; Shearer and Smith, 2012; Smith et al, 2014 2014; Stelma and Bhutta, 2014). …”

Section: Introductionmentioning

confidence: 99%

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

Locher

Groot

Iperen

et al. 2015

Developmental Neurobiology

View full text Add to dashboard Cite

Sensorineural hearing loss (SNHL) is one of the most common congenital disorders in humans, afflicting one in every thousand newborns. The majority is of heritable origin and can be divided in syndromic and nonsyndromic forms. Knowledge of the expression profile of affected genes in the human fetal cochlea is limited, and as many of the gene mutations causing SNHL likely affect the stria vascularis or cochlear potassium homeostasis (both essential to hearing), a better insight into the embryological development of this organ is needed to understand SNHL etiologies. We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9–W18) and show the cochlear expression dynamics of key potassium‐regulating proteins. At W12, MITF+/SOX10+/KIT+ neural‐crest‐derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na+/K+‐ATPase‐positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament. Finally, we investigated GJA1/CX43 and GJE1/CX23 expression, and suggest that GJE1 presents a potential new SNHL associated locus. Our study helps to better understand human cochlear development, provides more insight into multiple forms of hereditary SNHL, and suggests that human hearing does not commence before the third trimester of pregnancy. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1219–1240, 2015

show abstract

Non-syndromic hereditary sensorineural hearing loss: review of the genes involved

Abstract: This paper provides a concise overview of the currently known genes involved in non-syndromic hereditary hearing loss and their function in the inner ear.

Cited by 29 publications

References 88 publications

Whole exome sequencing identified a second pathogenic variant in HOMER2 for autosomal dominant non‐syndromic deafness

Whole exome sequencing identified a second pathogenic variant in HOMER2 for autosomal dominant non‐syndromic deafness

Different Phenotypes of the Two Chinese Probands with the Same c.889G>A (p.C162Y) Mutation in COCH Gene Verify Different Mechanisms Underlying Autosomal Dominant Nonsyndromic Deafness 9

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

Contact Info

Product

Resources

About