Coincidence of mutations in different connexin genes in Hungarian patients.
Mutations in the GJB2 gene are the most common cause of hereditary prelingual sensorineural hearing impairment in Europe. Several studies indicate that different members of the connexin protein family interact to form gap junctions in the inner ear. Mutations in different connexin genes may accumulate and, consequently lead to hearing impairment. Therefore, we screened 47 Hungarian GJB2- heterozygous (one mutation in coding exon of the GJB2 gene) patients with hearing impairment for DNA changes in two further connexin genes (GJB6 and GJB3) and in the 5' non-coding region of GJB2 including the splice sites. Eleven out of 47 GJB2-heterozygous patients analyzed carried the splice site mutation -3170G>A in the 5'UTR region of GJB2. One out of these 11 patients showed homozygous -3170G>A genotype in combination with p.R127H. Next to the GJB2 mutations we noted 2 cases of deletion in GJB6 [Delta(GJB6-D13S1830)] and 3 (2 new and 1 described) base substitutions in GJB3 [c.357C>T, c.798C>T and c.94C>T (p.R32W)] which are unlikely disease-causing. Our results suggest the importance of routine screening for the rather frequent -3170G>A mutation (in addition to c.35delG) in patients with hearing impairment.
Tóth
Tímea
T
Department of Otolaryngology, Medical and Health Science Center, University of Debrecen, 4012 Debrecen, Hungary. ttimi@dote.hu
Kupka
Susan
S
Haack
Birgit
B
Fazakas
Ferenc
F
Muszbek
Laszló
L
Blin
Nikolaus
N
Pfister
Markus
M
Sziklai
István
I
D020121:5' Untranslated Regions; D016022:Case-Control Studies; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006814:Hungary; D009154:Mutation; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D022821:RNA Splice Sites / Q000235:genetics; D017384:Sequence Deletion
D020121:5' Untranslated Regions; D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D022821:RNA Splice Sites; D000072259:Connexin 26; C068044:GJB3 protein, human