title: Functional analysis of a novel I71N mutation in the GJB2 gene among Southern Egyptians causing autosomal recessive hearing loss.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Assiut University, Assiut, Egypt.
authors.forename: Mostafa R
authors.initials: MR
authors.lastname: Mohamed
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Andreas
authors.initials: A
authors.lastname: Bress
authors.forename: Manuela
authors.initials: M
authors.lastname: Baur
authors.forename: Ragaa H M
authors.initials: RH
authors.lastname: Salama
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Bakr
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Mohamed
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Blin
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004534:Egypt / Q000453:epidemiology; D005787:Gene Frequency; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D017630:Connexins; C000607045:GJB2 protein, Xenopus; C000607042:GJB2 protein, human; D000072259:Connexin 26