PMID- 28974383
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20180905
IS  - 1878-5891 (Electronic)
IS  - 0378-5955 (Linking)
VI  - 355
DP  - 2017 Nov
TI  - A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related 
      hearing impairment.
PG  - 97-101
LID - S0378-5955(16)30408-7 [pii]
LID - 10.1016/j.heares.2017.09.013 [doi]
AB  - Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 
      (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS 
      and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly 
      inherited low-frequency sensorineural HI. These two phenotypes are clinically 
      distinct indicating that WFS1 is a reasonable candidate for genetic studies in 
      patients with other phenotypes of HI. Here we have investigated, whether the 
      variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). 
      WFS1 gene was investigated in a population sample of 518 Finnish adults born in 
      1938-1949 and representing variable hearing phenotypes. Identified variants were 
      evaluated with respect to pathogenic potential. A rare mutation predicted to be 
      pathogenic was found in a family with many members with impaired hearing. Twenty 
      members were recruited to a segregation study and a detailed clinical 
      examination. Heterozygous p.Tyr528His variant segregated completely with 
      late-onset HI in which hearing deteriorated first at high frequencies and 
      progressed to mid and low frequencies later in life. We report the first mutation 
      in the WFS1 gene causing late-onset HI with audiogram configurations typical for 
      ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list 
      of such genes.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Kytovuori, Laura
AU  - Kytovuori L
AD  - Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 
      Oulu, Finland; Research Unit of Clinical Neuroscience, University of Oulu, P.O. 
      Box 5000, FI-90014 Oulu, Finland; Department of Neurology, Oulu University 
      Hospital, P.O. Box 20, FI-90029 Oulu, Finland. Electronic address: 
      laura.kytovuori@oulu.fi.
FAU - Hannula, Samuli
AU  - Hannula S
AD  - Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 
      Oulu, Finland; Department of Otorhinolaryngology and Head and Neck Surgery, Oulu 
      University Hospital, P.O. Box 21, FI-90029 Oulu, Finland; PEDEGO Research Unit, 
      University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland.
FAU - Maki-Torkko, Elina
AU  - Maki-Torkko E
AD  - Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University 
      Hospital, P.O. Box 21, FI-90029 Oulu, Finland; Department of Clinical and 
      Experimental Medicine/Technical Audiology, Faculty of Health Sciences, Linkoping 
      University, S-581 85 Linkoping, Sweden; Department of ENT-Head Neck Surgery, 
      Region Ostergotland, Sweden.
FAU - Sorri, Martti
AU  - Sorri M
AD  - Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 
      Oulu, Finland; Department of Otorhinolaryngology and Head and Neck Surgery, Oulu 
      University Hospital, P.O. Box 21, FI-90029 Oulu, Finland; PEDEGO Research Unit, 
      University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland.
FAU - Majamaa, Kari
AU  - Majamaa K
AD  - Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 
      Oulu, Finland; Research Unit of Clinical Neuroscience, University of Oulu, P.O. 
      Box 5000, FI-90014 Oulu, Finland; Department of Neurology, Oulu University 
      Hospital, P.O. Box 20, FI-90029 Oulu, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170928
PL  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (Membrane Proteins)
RN  - 0 (wolframin protein)
SB  - IM
MH  - Acoustic Stimulation
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Age of Onset
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/genetics
MH  - Audiometry, Pure-Tone
MH  - DNA Mutational Analysis
MH  - Female
MH  - Finland
MH  - Genetic Predisposition to Disease
MH  - Hearing/*genetics
MH  - Hearing Loss, Sensorineural/diagnosis/*genetics/physiopathology
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - *Mutation
MH  - Pedigree
MH  - Phenotype
MH  - Presbycusis/diagnosis/*genetics/physiopathology
MH  - Young Adult
OTO - NOTNLM
OT  - Age-related hearing impairment
OT  - High-frequency hearing impairment
OT  - Presbyacusis
OT  - Wolfram syndrome
EDAT- 2017/10/05 06:00
MHDA- 2018/07/10 06:00
CRDT- 2017/10/05 06:00
PHST- 2016/09/07 00:00 [received]
PHST- 2017/03/12 00:00 [revised]
PHST- 2017/09/23 00:00 [accepted]
PHST- 2017/10/05 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/10/05 06:00 [entrez]
AID - S0378-5955(16)30408-7 [pii]
AID - 10.1016/j.heares.2017.09.013 [doi]
PST - ppublish
SO  - Hear Res. 2017 Nov;355:97-101. doi: 10.1016/j.heares.2017.09.013. Epub 2017 Sep 
      28.