OBJECTIVES : Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic recessive deafness or dominant hearing loss (HL) with or without keratoderma. The objective was to perform a molecular evaluation to establish the inherited pattern of deafness in the sporadic cases afferent to our center. METHODS: The subject was a 2-year-old Italian girl with nonsyndromic early onset HL. We performed DNA sequencing of the GJB2 gene and deletion analysis of the GJB6 gene in all family members. RESULTS: Direct sequencing of the gene showed a heterozygous C-->G transition at nucleotide 172 resulting in a proline to alanine amino acid substitution at codon 58 (P58A). The analyses indicate that the P58A mutation appeared de novo in the proband with a possible dominant effect. CONCLUSIONS: This mutation occurs in the first extracellular domain (EC1), which seems to be very important for connexon-connexon interaction and for the control of voltage gating of the channel. The de novo occurrence of an EC1 mutation in a sporadic case of deafness is consistent with the assumption that P58A can cause dominant HL.
|Titolo:||A new de novo missense mutation in connexin 26 in a sporadic case of nonsyndromic deafness|
|Parole Chiave:||Connexin 26; De novo mutation; Dominant deafness; P58A|
|Settore Scientifico Disciplinare:||Settore MED/32 - Audiologia|
|Data di pubblicazione:||mag-2007|
|Digital Object Identifier (DOI):||10.1097/MLG.0b013e31803330d9|
|Appare nelle tipologie:||01 - Articolo su periodico|