Corrigendum to: NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss

Abstract Hearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of near 13 cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in the NCOA3 gene (NM_181659, c.2810C > G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining and in situ hybridization showed expression of ncoa3 in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system. ncoa3−/− did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour in ncoa3−/−, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths of ncoa3−/− and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role of ncoa3 in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.

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Cellular and Molecular Mechanisms of Autosomal Dominant Form of Progressive Hearing Loss, DFNA2

Journal of Biological Chemistry ◽

10.1074/jbc.m110.179010 ◽

2010 ◽

Vol 286 (2) ◽

pp. 1517-1527 ◽

Cited By ~ 20

Author(s):

Hyo Jeong Kim ◽

Ping Lv ◽

Choong-Ryoul Sihn ◽

Ebenezer N. Yamoah

Keyword(s):

Hearing Loss ◽

Molecular Mechanisms ◽

Autosomal Dominant ◽

Progressive Hearing Loss ◽

Dominant Form ◽

Autosomal Dominant Form

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Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-onset Progressive Hearing Loss

Genes ◽

10.3390/genes11030273 ◽

2020 ◽

Vol 11 (3) ◽

pp. 273

Author(s):

Shin-ichiro Oka ◽

Timothy F. Day ◽

Shin-ya Nishio ◽

Hideaki Moteki ◽

Maiko Miyagawa ◽

...

Keyword(s):

Hearing Loss ◽

Clinical Characteristics ◽

Large Scale ◽

Autosomal Dominant ◽

Late Onset ◽

Site Directed Mutagenesis ◽

Molecular Characteristics ◽

Progressive Hearing Loss ◽

Cochlear Hair Cells

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

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ELMOD3, a novel causative gene, associated with human autosomal dominant nonsyndromic and progressive hearing loss

Human Genetics ◽

10.1007/s00439-018-1885-0 ◽

2018 ◽

Vol 137 (4) ◽

pp. 329-342 ◽

Cited By ~ 8

Author(s):

Wu Li ◽

Jie Sun ◽

Jie Ling ◽

Jiada Li ◽

Chufeng He ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Dominant ◽

Progressive Hearing Loss ◽

Causative Gene

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NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss

10.1101/2020.06.07.138909 ◽

2020 ◽

Author(s):

Rodrigo Salazar da Silva ◽

Vitor Lima Goes Dantas ◽

Leandro Ucela Alves ◽

Ana Carla Batissoco ◽

Jeanne Oiticica ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Dominant ◽

Snp Array ◽

Large Family ◽

Sensory Function ◽

Causative Mutation ◽

Linkage Data ◽

Potential Candidate ◽

Mineral Density ◽

Progressive Hearing Loss

AbstractHearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of 13cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in the NCOA3 gene (NM_181659, c.2810C>G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining and in situ hybridization showed expression of ncoa3 in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system. ncoa3−/− did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour in ncoa3−/−, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths of ncoa3−/− and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role of ncoa3 in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.

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Hearing Outcome of Stapes Surgery in NIENT, Bangladesh

Bangladesh Journal of Otorhinolaryngology ◽

10.3329/bjo.v26i1.47950 ◽

2020 ◽

Vol 26 (1) ◽

pp. 31-36

Author(s):

Md Zakaria Sarkar ◽

AHM Ferdows Nur ◽

Utpal Kumar Dutta ◽

Muhammad Rafiqul Islam ◽

Debabrota Roy ◽

...

Keyword(s):

Hearing Loss ◽

Cross Sectional Study ◽

Surgical Trauma ◽

Group 14 ◽

Progressive Hearing Loss ◽

Cross Sectional ◽

Hearing Gain ◽

Hearing Outcome

Objective: The aim of this study was to evaluate hearing outcome after stapedotomy in patients with Otosclerosis. Methods: This cross sectional study was carried out from July 2017 to January 2019 in National Institute of ENT, Unit V. About 22 patients with Otosclerosis were included in this study. Diagnosis of Otosclerosis was based on the history, medical status with Otoscopy, Tuning fork tests and Audiometric tests. We compiled data on the pre and post operative air-bone gap (ABG) at 0.5, 1, 2 KHZ. The ABG was Calculated using AC and BC thresholds on the same audiogram. Post operative hearing gain was then Calculated from the ABG before the operation minus the ABG of the last follow up examination Results: In this study most of the cases were age group 14-30 years (72.7%), female (54.5%). Most common symptoms was progressive hearing loss, tinnitus (77.8%).The average preoperative hearing loss in this study was (AC) was 48.31±7.68. The average post opt. hearing (AC) at follow up was 28.95±10.30 with an average hearing gain of 15.40±8.53 dB which was significant. The average pre-operative ABG was 28.99 dB ± 8.10. The average post opt. ABG was analyzed at 1 follow up showed ABG 13.18±8.09 dB which was found to be significant. Conclusion: Stapedotomy is an effective surgical procedure for the treatment of otosclerosis which leads to improvement in patient’s quality of life. A favorable hearing outcome can be obtained by the combination of experienced hands with minimal surgical trauma and appropriate surgical technique. Bangladesh J Otorhinolaryngol; April 2020; 26(1): 31-36

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