A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss

Noguchi, Yoshihiro; Yashima, Takatoshi; Hatanaka, Akio; Uzawa, Masamichi; Yasunami, Michio; Kimura, Akinori; Kitamura, Ken

doi:10.1080/00016480510044232

Cited by 19 publications

(6 citation statements)

References 23 publications

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“…The novel missense variant c.2530G > T (p.Ala844-Ser) identified in this study caused only nonsyndromic HL in this family. Interestingly, the variant with the substitution of A described in another independent family of nonsyndromic LFSNHL by Noguchi et al [31] is not only in the same codon but also in the same genomic position as the variant with the substitution of T detected in our study, evidently suggesting that the Ala844 residue of WFS1 may play an important role in NSHL. To date, neither the type nor location of the pathogenic variant could predict the phenotype [45].…”

Section: Discussionsupporting

confidence: 78%

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

Wang

Zhang

et al. 2022

BioMed Research International

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Background. Nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) is an uncommon form of hearing loss (HL) that typically affects frequencies at 2000 Hz and below. Heterozygous variants in the WFS1 gene at the DFNA6/14/38 locus are considered a common cause of LFSNHL. To date, 34 different pathogenic genetic variants have been reported to cause LFSNHL with seven of these variants identified in the Chinese population. However, limited reports are available on the association between WFS1 gene and LFSNHL. Here, we report a five-generation Chinese family with an autosomal dominant inheritance pattern of postlingual and progressive LFSNHL. Methods. Routine clinical and audiological examinations were performed on 16 affected and 7 healthy members in this family. The targeted next-generation sequencing of 127 known deafness genes was performed to identify variants in affected individuals. Sanger sequencing were further employed to confirm the pathogenic variant identified. Results. A novel heterozygous pathogenic genetic variant c.2530G > T (p.Ala844Ser) was identified in the WFS1 gene in all patients of this family. The mutated Ala residue is evolutionarily conserved and cosegregated with HL. The variant was predicted to be deleterious by MutationTaster, PolyPhen-2, LRT, and Fathmm software. Conservation analysis and 3D protein structure model indicated that the variant caused a structural change in the protein. Conclusions. Our present study identifies a novel heterozygous WFS1 variant associated with LFSNHL in a Chinese family.

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Section: Discussionsupporting

confidence: 78%

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

Wang

Zhang

et al. 2022

BioMed Research International

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“…Most of them cluster in the C‐terminal region of the WFS1 protein, as does E864K. However, the E864K mutation has never been described in the numerous series of non‐syndromic LFSNHI reported in the literature [3,14–19].…”

Section: Discussionmentioning

confidence: 99%

Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene

Valéro¹,

Bannwarth²,

Roman³

et al. 2008

Diabetic Medicine

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“…Genetic analyses in WS have identified a wide spectrum of mutations (Table 1; 5, 28, 29, 53, 72–112). In many patients, loss‐of‐function mutations such as stop, frameshift (40% of total) and splice site mutations were found, and missense mutations were detected in approximately 35% of the cases (28, 29, 74, 77, 113).…”

Section: Ws and Mutationsmentioning

confidence: 99%

Wolfram syndrome and WFS1 gene

2010

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Wolfram syndrome (WS) (MIM 222300) is a rare multisystem neurodegenerative disorder of autosomal recessive inheritance, also known as DIDMOAD (diabetes insipidus, insulin-deficient diabetes mellitus, optic atrophy and deafness). A Wolfram gene (WFS1) has been mapped to chromosome 4p16.1 which encodes an endoplasmic reticulum (ER) membrane-embedded protein. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium omeostasis. Disturbances or overloading of these functions induce ER stress responses, including apoptosis. Most WS patients carry mutations in this gene, but some studies provided evidence for genetic heterogeneity, and the genotype-phenotype relationships are not clear. Here we review the data regarding the mechanisms and the mutations of WFS1 gene that relate to WS.

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A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss

Cited by 19 publications

References 23 publications

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene

Wolfram syndrome and WFS1 gene

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