Search results for "Connexin 26"
showing 9 items of 9 documents
A genotype-phenotype correlation in Sicilian patients with GJB2 biallelic mutations
2015
The aim of this work was to study the genotype distribution of Sicilian patients with biallelic GJB2 mutations; to correlate genotype classes and/or specific mutations of GJB2 gene (35delG-non-35delG) with audiologic profiles. A total of 10 different mutations and 11 different genotypes were evidenced in 73 SNHL subjects; 35delG (90.36 % of cases) and IVS1+1 (13.69 %) were the most common mutations found in the cohort with a significant difference in the distribution between North and South Sicily. Audiological evaluation revealed a severe (16/73) to profound (47/73) hearing loss (HL) in 86.13 % of cases without significant difference between the degree of HL and the province of origin of t…
Intrafamilial variability of the deafness and goiter phenotype in Pendred syndrome caused by a T416P mutation in the SLC26A4 gene.
2004
AbstractPendred syndrome (PS) is the most common cause of syndromic deafness, accounting for more than 5% of all autosomal-recessive hearing loss cases. It is characterized by bilateral sensorineural hearing loss and by goiter with or without hypothyroidism. Mutations in the SLC26A4 gene cause both classical PS and deafness associated with an enlarged vestibular aqueduct without goiter.To investigate a possible genotype-phenotype correlation in PS, we performed a detailed clinical and genetic study in three adult German sibs with typical PS caused by a common homozygous SLC26A4 mutation, T416P. An audiological long-term follow-up of 23 yr showed that the mutation T416P is associated with a …
Identification of D179H, a novel missense GJB2 mutation in a Western Sicily family
2013
The main purpose of this study was to describe a novel missense mutation (p.D179H) found in a Western Sicily family and to examine the genetic and audiologic profiles of all family members by performing a GJB2 and GJB6 mutations analysis and a complete audiologic assessment. The proband was a 3-month-old infant with a congenital profound sensorineural hearing loss; direct sequencing of the GJB2 revealed the presence of a c.35delG mutation in the heterozygous state and a heterozygous G[C transition at nucleotide 535 in trans; this novel mutation, called p.D179H, resulted in an aspartic acid to histidine change at codon 179. It was also evidenced in the heterozygous state in two members of th…
Distribution and phenotype ofGJB2mutations in 102 Sicilian patients with congenital non syndromic sensorineural hearing loss
2014
Objective: To evaluate the frequency of GJB2 mutations and their correlation with phenotype in Sicilian non-syndromic sensorineural hearing loss (NSHL) patients. Design: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. Study sample: A cohort of 102 Sicilian NSHL patients. Results: Fifteen different mutations in GJB2 and seventeen different genotypes were detected. No GJB6 mutations were found. The hearing impairment was profound in the 64.72% of probands (mean PTA 0.25 – 4 kHz of 88.82 26.52 dB HL). A total of 81.37% of patients harboured at least one c.35delG allele; c.167delT and c…
Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations
2014
Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. Results: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic h…
Epidemiological study of nonsyndromic hearing loss in Sicilian newborns
2007
Deafness is caused by a variety of facts, genetic and environmental. Regarding the acquired causes, deafness can be the consequence of prenatal infections, acoustic or cerebral trauma, and the use of ototoxic drugs. Deafness can be the only manifestation (nonsyndromic forms) or it may occur together with other phenotypic findings (syndromic forms). The majority of nonsyndromicdeafness has a genetic basis [Van Camp et al., 1997]. In recent years, deafness and hearing loss have assumed a clinical importance in the study of congenital disorders [Morton et al., 1991]. The clinical interest for hearing loss is supported by the social impact that this disorder has; if not treated, delays in the d…
A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression
2010
Contains fulltext : 87760_1.pdf (author's version ) (Open Access) Contains fulltext : 87760_2.pdf (Publisher’s version ) (Closed access) Eleven affected members of a large German-American family segregating recessively inherited, congenital, non-syndromic sensorineural hearing loss (SNHL) were found to be homozygous for the common 35delG mutation of GJB2, the gene encoding the gap junction protein Connexin 26. Surprisingly, four additional family members with bilateral profound SNHL carried only a single 35delG mutation. Previously, we demonstrated reduced expression of both GJB2 and GJB6 mRNA from the allele carried in trans with that bearing the 35delG mutation in these four persons. Usin…
<i>GJB2</i> Mutations and Genotype-Phenotype Correlation in 335 Patients from Germany with Nonsyndromic Sensorineural Hearing Loss: Evide…
2009
We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated <i>GJB2</i> alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the <i>GJB6</i> gene. Eleven <i>GJB2</i> mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic <i>GJB2</i> mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic <i>GJB2</i> mutations typically ind…
Deficient membrane integration of the novel p.N14D-GJB2mutant associated with non-syndromic hearing impairment
2006
Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many o…