Open AccessFunctional Analysis of a Novel I71N Mutation in the <i>GJB2</i> Gene Among Southern Egyptians Causing Autosomal Recessive Hearing Loss
Author(s) -
Mostafa R. Mohamed,
Ioana Alesutan,
Michael Föller,
Mentor Sopjani,
Andreas Breß,
Manuela Baur,
Ragaa H. M. Salama,
Mohamed Salama Bakr,
Mohamed A. Mohamed,
Nikolaus Blin,
Florian Läng,
Markus Pfister
Publication year - 2010
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000324004
Subject(s) - genetics , hearing loss , mutation , biology , allele , gene , amino acid , xenopus , population , mutation frequency , microbiology and biotechnology , medicine , audiology , environmental health
Mutations in GJB2, a gene encoding the gap junction protein connexin 26 (Cx26), are a major cause for inherited and sporadic non-syndromic hearing loss, albeit with highly variable clinical effects. To determine new mutations and their frequencies in a Southern Egyptian population restriction fragment length polymorphism, gene sequencing, and single strand conformational polymorphism revealed only 2 mutations for GJB2: c.35delG and p.I71N. The allelic frequency of the c.35delG mutation was 8.7% (found in 27 out of 310 investigated alleles) resulting in a relatively low carrier frequency (1.6%) in Upper Egypt. The new mutation, a substitution of isoleucin (I) (a non-polar amino acid) by the polar amino acid asparagin (N), was localized within the conserved Cx26 structure. The functional significance of p.I71N was tested by injection of cRNA into Xenopus laevis oocytes. Cx26 hemi-channel activity was measured by depolarization activated conductance in non-coupled oocytes. As a result, the p.I71N mutated channel was non-functional. The study discloses a novel, functionally relevant GJB2 mutation and defines the contribution of Cx26 alterations to the hearing loss in the Southern Egyptian population.