title: GJB2 and GJB6 mutations in 165 Danish patients showing non-syndromic hearing impairment.
abstract: Thirty-two genes causing non-syndromic hearing impairment (NSHI) have been cloned, including GJB2 and GJB6 encoding the gap junction subunits connexin 26 and connexin 30, respectively. One mutation in GJB2, 35delG, accounts for a large percentage of GJB2 hearing impairment in Southern Europe whereas a considerably lower frequency has been reported from Northern European populations. Recently, a 342-kb deletion implicating GJB6 was found in 22 out of 44 NSHI patients of Spanish origin with only one mutated allele of GJB2. We report the first study of GJB2 and GJB6 mutations in Danish patients with NSHI. We tested 165 individuals and found GJB2 mutations in 16 individuals. The deletion implicating GJB6 was found in two individuals out of 9 heterozygous for GJB2 mutation. Furthermore, we screened 509 unselected samples from the Danish newborn population for the 35delG mutation in GJB2. We found 9 samples heterozygous for 35delG and 11 samples heterozygous for mutations leading to amino acid variants in GJB2 protein. In conclusion, our data are in accordance with results from other Northern European populations. Furthermore, our data on the GJB6 deletion suggest that routine screening for this deletion could help to explain hearing impairment in some Northern European NSHI patients heterozygous for a mutation in GJB2.
authors.affiliation: Department of Medical Genetics, John F. Kennedy Institute, DK-2600 Glostrup, Denmark. kag@kennedy.dk
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.forename: Lars Allan
authors.initials: LA
authors.lastname: Larsen
authors.forename: Nanna Dahl
authors.initials: ND
authors.lastname: Rendtorff
authors.forename: Agnete
authors.initials: A
authors.lastname: Parving
authors.forename: Bent
authors.initials: B
authors.lastname: Nørgaard-Pedersen
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D003718:Denmark; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26