PMID- 28545070
OWN - NLM
STAT- MEDLINE
DCOM- 20170915
LR  - 20190208
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel
      DNA sequencing-based analysis identified novel variants associated with autosomal
      dominant hearing loss.
PG  - e0177636
LID - 10.1371/journal.pone.0177636 [doi]
AB  - 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.
FAU - Kitano, Tomohiro
AU  - Kitano T
AD  - Department of Otorhinolaryngology, Shinshu University School of Medicine,
      Matsumoto, Japan.
FAU - Miyagawa, Maiko
AU  - Miyagawa M
AD  - Department of Otorhinolaryngology, Shinshu University School of Medicine,
      Matsumoto, Japan.
AD  - Department of Hearing Implant Sciences, Shinshu University School of Medicine,
      Matsumoto, Japan.
FAU - Nishio, Shin-Ya
AU  - Nishio SY
AD  - Department of Otorhinolaryngology, Shinshu University School of Medicine,
      Matsumoto, Japan.
AD  - Department of Hearing Implant Sciences, Shinshu University School of Medicine,
      Matsumoto, Japan.
FAU - Moteki, Hideaki
AU  - Moteki H
AD  - Department of Otorhinolaryngology, Shinshu University School of Medicine,
      Matsumoto, Japan.
AD  - Department of Hearing Implant Sciences, Shinshu University School of Medicine,
      Matsumoto, Japan.
FAU - Oda, Kiyoshi
AU  - Oda K
AD  - Department of Otorhinolaryngology, Tohoku Rosai Hospital, Sendai, Japan.
FAU - Ohyama, Kenji
AU  - Ohyama K
AD  - Department of Otorhinolaryngology, Tohoku Rosai Hospital, Sendai, Japan.
FAU - Miyazaki, Hiromitsu
AU  - Miyazaki H
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Tohoku University School
      of Medicine, Sendai, Japan.
FAU - Hidaka, Hiroshi
AU  - Hidaka H
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Tohoku University School
      of Medicine, Sendai, Japan.
FAU - Nakamura, Ken-Ichi
AU  - Nakamura KI
AD  - Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University
      School of Medicine, Shimotsuke, Japan.
FAU - Murata, Takaaki
AU  - Murata T
AD  - Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate
      School of Medicine, Maebashi, Japan.
FAU - Matsuoka, Rina
AU  - Matsuoka R
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine,
      Tokyo, Japan.
FAU - Ohta, Yoko
AU  - Ohta Y
AD  - Department of Otorhinolaryngology Head and Neck Surgery, Tokyo Medical
      University, Tokyo, Japan.
FAU - Nishiyama, Nobuhiro
AU  - Nishiyama N
AD  - Department of Otorhinolaryngology Head and Neck Surgery, Tokyo Medical
      University, Tokyo, Japan.
FAU - Kumakawa, Kozo
AU  - Kumakawa K
AD  - Department of Otorhinolaryngology, Toranomon Hospital, Tokyo, Japan.
FAU - Furutate, Sakiko
AU  - Furutate S
AD  - Department of Otorhinolaryngology, International University of Health and
      Welfare, Mita Hospital, Tokyo, Japan.
FAU - Iwasaki, Satoshi
AU  - Iwasaki S
AD  - Department of Otorhinolaryngology, International University of Health and
      Welfare, Mita Hospital, Tokyo, Japan.
FAU - Yamada, Takechiyo
AU  - Yamada T
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, University of Fukui,
      Fukui, Japan.
FAU - Ohta, Yumi
AU  - Ohta Y
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University
      Graduate School of Medicine, Osaka, Japan.
FAU - Uehara, Natsumi
AU  - Uehara N
AD  - Department of Otolaryngology-Head and Neck Surgery, Kobe University School of
      Medicine, Kobe, Japan.
FAU - Noguchi, Yoshihiro
AU  - Noguchi Y
AD  - Department of Hearing Implant Sciences, Shinshu University School of Medicine,
      Matsumoto, Japan.
FAU - Usami, Shin-Ichi
AU  - Usami SI
AUID- ORCID: http://orcid.org/0000-0002-5068-6122
AD  - Department of Otorhinolaryngology, Shinshu University School of Medicine,
      Matsumoto, Japan.
AD  - Department of Hearing Implant Sciences, Shinshu University School of Medicine,
      Matsumoto, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170517
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Codon, Nonsense)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (POU4F3 protein, human)
RN  - 0 (Transcription Factor Brn-3C)
RN  - 9007-49-2 (DNA)
RN  - Deafness, Autosomal Dominant 15
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Asian Continental Ancestry Group/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Codon, Nonsense
MH  - DNA/chemistry/metabolism
MH  - Female
MH  - Frameshift Mutation
MH  - Gene Frequency
MH  - Hearing Loss, Sensorineural/*genetics/pathology
MH  - High-Throughput Nucleotide Sequencing
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Sequence Analysis, DNA
MH  - Transcription Factor Brn-3C/*genetics
MH  - Young Adult
PMC - PMC5435223
EDAT- 2017/05/26 06:00
MHDA- 2017/09/16 06:00
CRDT- 2017/05/26 06:00
PHST- 2016/12/26 00:00 [received]
PHST- 2017/05/01 00:00 [accepted]
PHST- 2017/05/26 06:00 [entrez]
PHST- 2017/05/26 06:00 [pubmed]
PHST- 2017/09/16 06:00 [medline]
AID - 10.1371/journal.pone.0177636 [doi]
AID - PONE-D-16-51101 [pii]
PST - epublish
SO  - PLoS One. 2017 May 17;12(5):e0177636. doi: 10.1371/journal.pone.0177636.
      eCollection 2017.