A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings

Bramhall, Naomi F.; Kallman, Jeremy C.; Verrall, Aimee M.; Street, Valerie A.

doi:10.1186/1471-2350-9-48

Cited by 16 publications

(7 citation statements)

References 35 publications

(35 reference statements)

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“…The KNUF46 family had low-to-mid-frequency non-syndromic hearing loss (Additional file 2 : Figure S1). This type of hearing loss is uncommon and has been associated with only the DIAPH1 , MYO7A and WFS1 genes [ 21 ]. Interestingly, we identified the missense mutation, p.P678S of DIAPH1 in this family (Figure 2 d), and it showed coincident audiographical configuration with known DFNA1 ( DIAPH1 ) hearing loss.…”

Section: Resultsmentioning

confidence: 99%

Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families

Baek

Dong-Bin

et al. 2012

Orphanet J Rare Dis

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BackgroundHereditary hearing loss is one of the most common heterogeneous disorders, and genetic variants that can cause hearing loss have been identified in over sixty genes. Most of these hearing loss genes have been detected using classical genetic methods, typically starting with linkage analysis in large families with hereditary hearing loss. However, these classical strategies are not well suited for mutation analysis in smaller families who have insufficient genetic information.MethodsEighty known hearing loss genes were selected and simultaneously sequenced by targeted next-generation sequencing (NGS) in 8 Korean families with autosomal dominant non-syndromic sensorineural hearing loss.ResultsFive mutations in known hearing loss genes, including 1 nonsense and 4 missense mutations, were identified in 5 different genes (ACTG1, MYO1F, DIAPH1, POU4F3 and EYA4), and the genotypes for these mutations were consistent with the autosomal dominant inheritance pattern of hearing loss in each family. No mutational hot-spots were revealed in these Korean families.ConclusionTargeted NGS allowed for the detection of pathogenic mutations in affected individuals who were not candidates for classical genetic studies. This report is the first documenting the effective use of an NGS technique to detect pathogenic mutations that underlie hearing loss in an East Asian population. Using this NGS technique to establish a database of common mutations in Korean patients with hearing loss and further data accumulation will contribute to the early diagnosis and fundamental therapies for hereditary hearing loss.

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Section: Resultsmentioning

confidence: 99%

Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families

Baek

Dong-Bin

et al. 2012

Orphanet J Rare Dis

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“…However, there have been no other studies reporting vertiginous symptoms in DFNA6/14/38 patients. Furthermore, studies on vestibular function, including caloric testing and vestibular evoked myogenic potentials, showed normal function [ 7 , 8 , 52 ]. In this study, seven individuals suffered from vertigo/dizziness; however, none of them underwent vestibular function testing.…”

Section: Discussionmentioning

confidence: 99%

WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis

et al. 2018

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A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.

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“…The progressive nature of DFNA6/14/38 hearing loss suggests a role for Wolframin in maintenance of sound transduction, rather than in the development and maturation of the cochlear cells. LFSNHL is thought to be a specific audiometric configuration indicative of endolymphatic hydrops (Bramhall et al, 2008). The proband of family BJ-L046 was evaluated with EcochG, and was found to have a bilaterally elevated SP/AP ratio, Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss

Sun

Cheng

et al. 2011

Journal of Genetics and Genomics

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A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings

Cited by 16 publications

References 35 publications

Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families

Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families

WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis

Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss

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