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

Masafumi Kobayashi, Maiko Miyagawa, Shin ya Nishio, Hideaki Moteki, Taro Fujikawa, Kenji Ohyama, Hirofumi Sakaguchi, Ikuyo Miyanohara, Akiko Sugaya, Yasushi Naito, Shin ya Morita, Yukihiko Kanda, Masahiro Takahashi, Kotaro Ishikawa, Yuki Nagano, Tetsuya Tono, Chie Oshikawa, Chiharu Kihara, Haruo Takahashi, Yoshihiro NoguchiShin ichi Usami

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0193359
JournalPLoS One
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Wolfram Syndrome
tungsten
High-Throughput Nucleotide Sequencing
Tungsten
Audition
hearing
DNA Sequence Analysis
Hearing Loss
Screening
sequence analysis
Genes
screening
mutation
Mutation
DNA
genes
High-Frequency Hearing Loss
Tinnitus
Haplotypes
signs and symptoms (animals and humans)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kobayashi, M., Miyagawa, M., Nishio, S. Y., Moteki, H., Fujikawa, T., Ohyama, K., ... Usami, S. I. (2018). WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis. PLoS One, 13(3), [e0193359]. https://doi.org/10.1371/journal.pone.0193359

WFS1 mutation screening in a large series of Japanese hearing loss patients : Massively parallel DNA sequencing-based analysis. / Kobayashi, Masafumi; Miyagawa, Maiko; Nishio, Shin ya; Moteki, Hideaki; Fujikawa, Taro; Ohyama, Kenji; Sakaguchi, Hirofumi; Miyanohara, Ikuyo; Sugaya, Akiko; Naito, Yasushi; Morita, Shin ya; Kanda, Yukihiko; Takahashi, Masahiro; Ishikawa, Kotaro; Nagano, Yuki; Tono, Tetsuya; Oshikawa, Chie; Kihara, Chiharu; Takahashi, Haruo; Noguchi, Yoshihiro; Usami, Shin ichi.

In: PLoS One, Vol. 13, No. 3, e0193359, 01.03.2018.

Research output: Contribution to journalArticle

Kobayashi, M, Miyagawa, M, Nishio, SY, Moteki, H, Fujikawa, T, Ohyama, K, Sakaguchi, H, Miyanohara, I, Sugaya, A, Naito, Y, Morita, SY, Kanda, Y, Takahashi, M, Ishikawa, K, Nagano, Y, Tono, T, Oshikawa, C, Kihara, C, Takahashi, H, Noguchi, Y & Usami, SI 2018, 'WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis', PLoS One, vol. 13, no. 3, e0193359. https://doi.org/10.1371/journal.pone.0193359
Kobayashi, Masafumi ; Miyagawa, Maiko ; Nishio, Shin ya ; Moteki, Hideaki ; Fujikawa, Taro ; Ohyama, Kenji ; Sakaguchi, Hirofumi ; Miyanohara, Ikuyo ; Sugaya, Akiko ; Naito, Yasushi ; Morita, Shin ya ; Kanda, Yukihiko ; Takahashi, Masahiro ; Ishikawa, Kotaro ; Nagano, Yuki ; Tono, Tetsuya ; Oshikawa, Chie ; Kihara, Chiharu ; Takahashi, Haruo ; Noguchi, Yoshihiro ; Usami, Shin ichi. / WFS1 mutation screening in a large series of Japanese hearing loss patients : Massively parallel DNA sequencing-based analysis. In: PLoS One. 2018 ; Vol. 13, No. 3.
@article{6d54a608c2ef42eaa9f50b692de587a7,
title = "WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis",
abstract = "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.",
author = "Masafumi Kobayashi and Maiko Miyagawa and Nishio, {Shin ya} and Hideaki Moteki and Taro Fujikawa and Kenji Ohyama and Hirofumi Sakaguchi and Ikuyo Miyanohara and Akiko Sugaya and Yasushi Naito and Morita, {Shin ya} and Yukihiko Kanda and Masahiro Takahashi and Kotaro Ishikawa and Yuki Nagano and Tetsuya Tono and Chie Oshikawa and Chiharu Kihara and Haruo Takahashi and Yoshihiro Noguchi and Usami, {Shin ichi}",
year = "2018",
month = "3",
day = "1",
doi = "10.1371/journal.pone.0193359",
language = "English",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - WFS1 mutation screening in a large series of Japanese hearing loss patients

T2 - Massively parallel DNA sequencing-based analysis

AU - Kobayashi, Masafumi

AU - Miyagawa, Maiko

AU - Nishio, Shin ya

AU - Moteki, Hideaki

AU - Fujikawa, Taro

AU - Ohyama, Kenji

AU - Sakaguchi, Hirofumi

AU - Miyanohara, Ikuyo

AU - Sugaya, Akiko

AU - Naito, Yasushi

AU - Morita, Shin ya

AU - Kanda, Yukihiko

AU - Takahashi, Masahiro

AU - Ishikawa, Kotaro

AU - Nagano, Yuki

AU - Tono, Tetsuya

AU - Oshikawa, Chie

AU - Kihara, Chiharu

AU - Takahashi, Haruo

AU - Noguchi, Yoshihiro

AU - Usami, Shin ichi

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85043786473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043786473&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0193359

DO - 10.1371/journal.pone.0193359

M3 - Article

C2 - 29529044

AN - SCOPUS:85043786473

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e0193359

ER -