The controversial p.Arg127His mutation in GJB2: report on three Portuguese hearing loss family cases.
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.
Matos
Tiago D
TD
Faculty of Science, Centre for Biodiversity, Functional, and Integrative Genomics (BioFIG), University of Lisbon, Lisbon, Portugal.
Simões-Teixeira
Helena
H
Caria
Helena
H
Rosa
Helena
H
O'Neill
Assunção
A
Fialho
Graça
G
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
D017630:Connexins; D017931:DNA Primers; C000607042:GJB2 protein, human; D000072259:Connexin 26