title: The controversial p.Arg127His mutation in GJB2: report on three Portuguese hearing loss family cases.
abstract: Mutations in the GJB2 gene account for up to 50% of hereditary nonsyndromic hearing loss in several populations. Over 200 mutations are already described in this gene, and three of them, c.35delG, c.167delT, and c.235delC, are the most frequent in Caucasians, Ashkenazi Jews, and Asians, respectively. Most of GJB2 hearing loss-related mutations are recessive, but a few dominant alleles have also been described. Apart from the clearly pathogenic mutations, there are some other variants whose pathogenicity is still controversial, such as p.Met34Thr, p.Val37Ile, p.Arg127His, and p.Val153Ile. The p.Arg127His allele has been found in some mono- and biallelic hearing-impaired patients from several countries. In this article we report on some Portuguese patients harboring this mutation. Taking into consideration the analysis of these Portuguese cases as well as the genetic and functional data regarding p.Arg127His available in the literature, we conclude that this variant may be a cause of hearing loss depending on environmental factors and/or genetic background.
authors.affiliation: Faculty of Science, Centre for Biodiversity, Functional, and Integrative Genomics (BioFIG), University of Lisbon, Lisbon, Portugal.
authors.forename: Tiago D
authors.initials: TD
authors.lastname: Matos
authors.forename: Helena
authors.initials: H
authors.lastname: Simões-Teixeira
authors.forename: Helena
authors.initials: H
authors.lastname: Caria
authors.forename: Helena
authors.initials: H
authors.lastname: Rosa
authors.forename: Assunção
authors.initials: A
authors.lastname: O'Neill
authors.forename: Graça
authors.initials: G
authors.lastname: Fialho
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003241:Consanguinity; D017931:DNA Primers / Q000235:genetics; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011174:Portugal
chemical_list: D017630:Connexins; D017931:DNA Primers; C000607042:GJB2 protein, human; D000072259:Connexin 26