Primignani Paola, Trotta Luca, Castorina Pierangela, Lalatta Faustina, Cuda Domenico, Murri Alessandra, Ambrosetti Umberto, Cesarani Antonio, Curcio Cristina, Coviello Domenico, Travi Maurizio
Laboratorio di Genetica Medica, Settore di Genetica Molecolare, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy.
Laryngoscope. 2007 May;117(5):821-4. doi: 10.1097/MLG.0b013e31803330d9.
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.
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.
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.
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.
