TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

Moteki, Hideaki; Nishio, Shin‐ya; Hashimoto, Shingo; Takumi, Yutaka; Iwasaki, Satoshi; Takeichi, Nobuhiko; Fukuda, Satoshi; Usami, Shin‐ichi

doi:10.1038/jhg.2012.73

Cited by 32 publications

(22 citation statements)

References 16 publications

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“…The incidence of POU4F3 variants was 0.6% (15/2,549) among the families with hereditary HL, and 2.5% (15/602) among the families with autosomal dominant HL in the Japanese population. This finding shows that POU4F3 variants represent the third largest cause of autosomal dominant HL in Japan, following KCNQ4 variants (6.6%) [36] and TECTA variants (2.9%) [37]. Therefore, POU4F3 is an important deafness gene in autosomal dominant HL patients, particularly in patients with mid- or high-frequency HL.…”

Section: Discussionmentioning

confidence: 97%

POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss

et al. 2017

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A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands) to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants) were successfully identified in 15 probands (2.5%) among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants in POU4F3 were a common cause of autosomal dominant HL.

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Section: Discussionmentioning

confidence: 97%

POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss

et al. 2017

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“…Previously, various mutations in the ZP domain (C1837G, R2021H, and Y1870C) of TECTA had been shown within the cytoplasm, suggesting the defect for the mutants to be secreted outside of the cell properly [20]. It seems likely that the p.Asp2006Tyr mutation in the ZP domain from this study might also cause similar defects in the secretion of α -tectorin.…”

Section: Discussionmentioning

confidence: 50%

A rare novel mutation in TECTA causes autosomal dominant nonsyndromic hearing loss in a Mongolian family

et al. 2014

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BackgroundThe genetic basis of autosomal dominant nonsyndromic hearing loss is complex. Genetic factors are responsible for approximately 50% of cases with congenital hearing loss. However, no previous studies have documented the clinical phenotype and genetic basis of autosomal dominant nonsyndromic hearing loss in Mongolians.MethodsIn this study, we performed exon capture sequencing of a Mongolian family with hereditary hearing loss and identified a novel mutation in TECTA gene, which encodes α -tectorin, a major component of the inner ear extracellular matrix that contacts the specialized sensory hair cells.ResultsThe novel G → T missense mutation at nucleotide 6016 results in a substitution of amino acid aspartate at 2006 with tyrosine (Asp2006Tyr) in a highly conserved zona pellucida (ZP) domain of α-tectorin. The mutation is not found in control subjects from the same family with normal hearing and a genotype-phenotype correlation is observed.ConclusionA novel missense mutation c.6016 G > T (p.Asp2006Tyr) of TECTA gene is a characteristic TECTA-related mutation which causes autosomal dominant nonsyndromic hearing loss. Our result indicated that mutation in TECTA gene is responsible for the hearing loss in this Mongolian family.

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“…KCNQ4 is one of the most frequently observed responsible genes for ADNSHL in the Japanese population, and its prevalence is 6.6% 39 . Likewise, the prevalence of ADNSHL caused by TECTA variants is 2.9%, 2.7% for POU4F3 variants, and 2.5% for WFS1 variants [40][41][42] .…”

Section: Discussionmentioning

confidence: 97%

Prevalence and clinical features of hearing loss caused by EYA4 variants

Shinagawa

Moteki

Nishio

et al. 2020

Sci Rep

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13 , takashi ishino 14 , natsumi Uehara 15 & Shin-ichi Usami 1,2* Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports. Hearing loss is the most common sensory disorder and more than 50% of cases of congenital or early onset hearing loss are caused by genetic factors 1. Regarding hereditary hearing loss, over 100 genes are known to be causative based on genetic analysis [Hereditary Hearing Loss Homepage: https://hereditaryhearingloss.org/ accessed

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TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

Cited by 32 publications

References 16 publications

POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss

POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss

A rare novel mutation in TECTA causes autosomal dominant nonsyndromic hearing loss in a Mongolian family

Prevalence and clinical features of hearing loss caused by EYA4 variants

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