A new de novo missense mutation in connexin 26 in a sporadic case of nonsyndromic deafness.
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.
Primignani
Paola
P
Laboratorio di Genetica Medica, Settore di Genetica Molecolare, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy. paola.primignani@policlinico.mi.it
Trotta
Luca
L
Castorina
Pierangela
P
Lalatta
Faustina
F
Cuda
Domenico
D
Murri
Alessandra
A
Ambrosetti
Umberto
U
Cesarani
Antonio
A
Curcio
Cristina
C
Coviello
Domenico
D
Travi
Maurizio
M
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
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26