title: A new de novo missense mutation in connexin 26 in a sporadic case of nonsyndromic deafness.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratorio di Genetica Medica, Settore di Genetica Molecolare, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy. paola.primignani@policlinico.mi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Primignani
authors.forename: Luca
authors.initials: L
authors.lastname: Trotta
authors.forename: Pierangela
authors.initials: P
authors.lastname: Castorina
authors.forename: Faustina
authors.initials: F
authors.lastname: Lalatta
authors.forename: Domenico
authors.initials: D
authors.lastname: Cuda
authors.forename: Alessandra
authors.initials: A
authors.lastname: Murri
authors.forename: Umberto
authors.initials: U
authors.lastname: Ambrosetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Cesarani
authors.forename: Cristina
authors.initials: C
authors.lastname: Curcio
authors.forename: Domenico
authors.initials: D
authors.lastname: Coviello
authors.forename: Maurizio
authors.initials: M
authors.lastname: Travi
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26