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
N1 - Funding Information:
This study was supported by a Health and Labour Sciences Research Grant for Research on rare and intractable diseases (H24-Nanchito (Nan)-Ippan-032) and Comprehensive Research on Disability Health and Welfare (H25-Kanakaku-Ippan-002) from the Ministry of Health, Labour and Welfare of Japan (to S.U.), by a Grant-in-Aid from Japan Agency for Medical Research and Development (to S.U.) (16ek0109114h0002, 16kk0205010h001), and by a Grant-in-Aid for Scientific Research (A) (22249057) from the Ministry of Education, Science and Culture of Japan (to S.U.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank the probands and their family members who participated in this study. This study was supported by a Health and Labour Sciences Research Grant for Research on rare and intractable diseases (H24-Nanchito(Nan)-Ippan-032) and Comprehensive Research on Disability Health and Welfare (H25-Kanakaku-Ippan-002) from the Ministry of Health, Labour and Welfare of Japan (S.U.), by a Grant-in-Aid from Japan Agency for Medical Research and Development (S.U.) (16ek0109114h0002, 16kk0205010h001), and by a Grant-in-Aid for Scientific Research (A) (22249057) from the Ministry of Education, Science and Culture of Japan (S.U.).
Publisher Copyright:
© 2018 Kobayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/3
Y1 - 2018/3
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.
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U2 - 10.1371/journal.pone.0193359
DO - 10.1371/journal.pone.0193359
M3 - Article
C2 - 29529044
AN - SCOPUS:85043786473
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 3
M1 - e0193359
ER -