title: GJB2 mutations in patients with non-syndromic hearing loss from Northeastern Hungary.
abstract: Mutations in the GJB2 gene encoding the gap-junction protein connexin 26 have been identified in many patients with childhood hearing impairment (HI). One single mutation, c.35delG, accounts for the majority of mutations in Caucasian patients with HI. In the present study we screened 500 healthy control individuals and a group of patients with HI from Northeastern Hungary for GJB2 mutations. The patients' group consisted of 102 familial from 28 families and 92 non-familial cases. The most common mutation in the Hungarian population is the c.35delG, followed by the c.71G>A (p.W24X) mutation. 34.3% of the patients in the familial group were homozygous, and 17.6% heterozygous for 35delG. In the non-familial group the respective values were 37% and 18% (allele frequency: 46.2%). In the general population an allele frequency of 2.4% was determined. Several patients were identified with additional, already described or new GJB2 mutations, mostly in heterozygous state. The mutation c.380G>A (p.R127H) was formerly found only in heterozygous state and its disease relation was controversial. We demonstrated the presence of this mutation in a family with three homozygous patients and 4 heterozygous unaffected family members, a clear indication of recessively inherited HI. Furthermore, we provided evidence for the pathogenic role of two new mutations, c.51C>A (p.S17Y) and c.177G>T (p.G59V), detected in the present study. In the latter case the pattern of inheritance might be dominant. Our results confirm the importance of GJB2 mutations in the Hungarian population displaying mutation frequencies that are comparable with those in the Mediterranean area.
authors.affiliation: Medical and Health Science Center, Department of Otolaryngology, University of Debrecen, Hungary.
authors.forename: Tímea
authors.initials: T
authors.lastname: Tóth
authors.forename: Susan
authors.initials: S
authors.lastname: Kupka
authors.forename: Birgit
authors.initials: B
authors.lastname: Haack
authors.forename: Kathrin
authors.initials: K
authors.lastname: Riemann
authors.forename: Simone
authors.initials: S
authors.lastname: Braun
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fazakas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Zenner
authors.forename: László
authors.initials: L
authors.lastname: Muszbek
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Blin
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.forename: István
authors.initials: I
authors.lastname: Sziklai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D006814:Hungary; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26