A genotype–phenotype correlation in Sicilian patients with GJB2 biallelic mutations

Abstract

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 the subjects (P = 0.727). The homozygous truncating (T/T) genotype was the most widespread (89.04 % of cases), with a severe-to-profound hearing impairment in 90.36 % of T/T class with respect to truncating/non-truncating (T/NT) and non-truncating/non-truncating (NT/NT) genotypes (P = 0.012). From the comparison of homozygous 35delG and 35delG/non-35delG genotypes, a more profound HL in the homozygous 35delG than in compound heterozygous 35delG/non-35delG (p < 0.0001) resulted. This study confirms that 35delG is the most common mutation in the Mediterranean area with a heterogeneous distribution of the genotypes between North and South Sicily; probands homozygotes for 35delG or presenting a T/T genotype are more apt to have a severe-to-profound HL.

Prevalence of Deafness‐Associated Connexin‐26 (GJB2) and Connexin‐30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily

“…In our study, the c.35delG allele accounted for 65.5% of mutated chromosomes, which is in accordance with data previously reported for Southern Europe and the Mediterranean area (Antoniadi et al., ; Gasparini et al., ), but it is in contrast with a higher c.35delG prevalence of 90.36% and 76.3% found in Western Sicily (Martines et al., ; Salvago et al., ). There are several possible explanations for the different distribution of c.35delG allele between the Sicilian geographic areas.…”

“…This data is in accordance with the findings that have been previously reported in other Italian studies (Primignani et al., ). However, a recent study in Western Sicily reported 65.75% of homozygous patients and 24.61% of compound heterozygous patients (Martines et al., ). In particular, all recruited probands from the Agrigento area were carriers of at least one c.35delG allele.…”

“…In the past, this genotype was associated with a profound HL in 65.79% and 64% of patients (Snoeckx et al., ; Berto et al., ). Our findings overlap those obtained by Martines et al (), who found HL in 75% of patients homozygous for the c.35delG allele.…”

“…In contrast, the second most frequent allele found in HL patients from Western Sicily was c.−23+1G>A (13.6% vs 2.9% of our study; Martines et al., ). This suggests a lower involvement in Eastern Sicily of the c.−23+1G>A allele.…”