Analysis of the GJB2 and GJB6 genes in Italian patients with nonsyndromic hearing loss: frequencies, novel mutations, genotypes, and degree of hearing loss.
Mutations in the GJB2 gene, which encodes the gap-junction protein connexin 26, are the most common cause of nonsyndromic hearing loss (NSHL) and account for about 32% of cases. We analyzed 734 patients and identified mutations in 474/1468 chromosomes. Thirty-six different mutations and five polymorphisms were found in 269 NSHL subjects. Our data confirm 35delG as the most frequent GJB2 mutation in the Italian population, accounting for about 68% of all the mutated GJB2 alleles analyzed. We also identified two novel variants: the V156I mutation and the C>A change at nucleotide 684 in the 3'UTR of the gene. The GJB6 gene deletion, del(GJB6-D13S1830), which can cause HL in combination with GJB2 mutations in trans, was identified in three patients, while the del(GJB6-D13S1854) was not observed in our cohort of patients. We collected audiometric data from 200 patients with biallelic DFNB1 mutations or with dominant mutation in GJB2 to determine the degree of HL to correlate the genotypes with the audiological phenotypes.
Primignani
Paola
P
Laboratorio di Genetica Medica, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena-Milano, Milan, Italy. paola.primignani@policlinico.mi.it
Trotta
Luca
L
Castorina
Pierangela
P
Lalatta
Faustina
F
Sironi
Francesca
F
Radaelli
Chiara
C
Degiorgio
Dario
D
Curcio
Cristina
C
Travi
Maurizio
M
Ambrosetti
Umberto
U
Cesarani
Antonio
A
Garavelli
Livia
L
Formigoni
Patrizia
P
Milani
Donatella
D
Murri
Alessandra
A
Cuda
Domenico
D
Coviello
Domenico Antonio
DA
D017677:Age Distribution; D000483:Alleles; D001299:Audiometry; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D005799:Genes, Dominant; D005808:Genes, Recessive; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D009154:Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics*
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26