title: WFS1 mutations in hearing-impaired children.
abstract: OBJECTIVE
  Mutations in the WFS1 gene can cause Wolfram syndrome or nonsyndromic hearing impairment (HI). The objective of this study was to ascertain the presence of mutations in WFS1 among children with HI from unknown causes.
  
  
  METHODS
  We screened 105 Finnish children with HI for mutations in exon 8 in WFS1.
  
  
  METHODS
  Children were born in a defined area in Northern Finland and they had sensorineural, mild to profound, syndromic, or nonsyndromic HI. They were negative for GJB2 mutations and for the m.1555A> G and m.3243A> G mutations in mitochondrial DNA.
  
  
  RESULTS
  We found three rare variants and the novel p.Gly831Ser variant in WFS1. Segregation analysis suggested that the novel variant had arisen de novo. The p.Gly831Ser variant may be a new member to the group of heterozygous WFS1 mutations that lead to HI, while the pathogenicity of the rare variant p.Gly674Arg remained unclear. The other two rare variants, p.Glu385Lys and p.Glu776Val, did not segregate with HI in the families.
  
  
  CONCLUSIONS
  WFS1 gene mutations are a rare cause of HI among Finnish children with HI.
authors.affiliation: * Department of Otorhinolaryngology, Oulu University Hospital , Oulu , Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Häkli
authors.forename: Laura
authors.initials: L
authors.lastname: Kytövuori
authors.forename: Mirja
authors.initials: M
authors.lastname: Luotonen
authors.forename: Martti
authors.initials: M
authors.lastname: Sorri
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005091:Exons; D005260:Female; D005387:Finland; D005820:Genetic Testing / Q000379:methods; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D019986:Persons with Hearing Disabilities; D010641:Phenotype; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C114987:wolframin protein; D000072259:Connexin 26
keywords: DFNA6/14/38; Wolframin; deafness; genetic; hearing loss; hereditary