title: High carrier frequency of the 35delG deafness mutation in European populations. Genetic Analysis Consortium of GJB2 35delG.
abstract: Congenital deafness accounts for about 1 in 1000 infants and approximately 80% of cases are inherited as an autosomal recessive trait. Recently, it has been demonstrated that connexin 26 (GJB2) gene is a major gene for congenital sensorineural deafness. A single mutation (named 35delG) was found in most recessive families and sporadic cases of congenital deafness, among Caucasoids, with relative frequencies ranging from 28% to 63%. We present here the analysis of the 35delG mutation in 3270 random controls from 17 European countries. We have detected a carrier frequency for 35delG of 1 in 35 in southern Europe and 1 in 79 in central and northern Europe. In addition, 35delG was detected in five out of 376 Jewish subjects of different origin, but was absent in other non-European populations. The study suggests either a single origin for 35delG somewhere in Europe or in the Middle East, and the possible presence of a carrier advantage together with a founder effect. The 35delG carrier frequency of 1 in 51 in the overall European population clearly indicates that this genetic alteration is a major mutation for autosomal recessive deafness in Caucasoids. This finding should facilitate diagnosis of congenital deafness and allow early treatment of the affected subjects.
authors.affiliation: Servizio di Genetica Medica, Ospedale Casa Sollievo de la Sofrenza, San Giovanni Rotondo, Italy. GENETCSS@FG.NETTUNO.IT
authors.forename: P
authors.initials: P
authors.lastname: Gasparini
authors.forename: R
authors.initials: R
authors.lastname: Rabionet
authors.forename: G
authors.initials: G
authors.lastname: Barbujani
authors.forename: S
authors.initials: S
authors.lastname: Melçhionda
authors.forename: M
authors.initials: M
authors.lastname: Petersen
authors.forename: K
authors.initials: K
authors.lastname: Brøndum-Nielsen
authors.forename: A
authors.initials: A
authors.lastname: Metspalu
authors.forename: E
authors.initials: E
authors.lastname: Oitmaa
authors.forename: M
authors.initials: M
authors.lastname: Pisano
authors.forename: P
authors.initials: P
authors.lastname: Fortina
authors.forename: L
authors.initials: L
authors.lastname: Zelante
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000097:blood; D004252:DNA Mutational Analysis; D003638:Deafness / Q000151:congenital* / Q000235:genetics; D005060:Europe; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004247:DNA