Screening for the GJB2 c.-3170 G>A (IVS 1+1 G>A) Mutation in Brazilian Deaf Individuals Using Multiplex Ligation–Dependent Probe Amplification

Abstract

Mutations in GJB2 gene are the most common cause of nonsyndromic sensorineural recessive hearing loss. One specific mutation, c.35delG, is the most frequent in the majority of Caucasian populations and may account for up to 70% of all GJB2 mutations. However, 10-40% of the patients carry only one pathogenic mutation in the GJB2 gene. Deletions del(GJB6-D13S1830) and del(GJB6-D13S1854), truncating the GJB6 gene, have been detected in GJB2 heterozygous patients in different populations. The IVS 1+1 G>A splice site mutation in the noncoding region of the GJB2 gene has been found in heterozygous state in addition to c.35delG mutation. This mutation has not been reported in Brazilian deaf patients. In the present study we investigated the presence of the IVS 1+1 G>A mutation by multiplex ligation-dependent probe amplification in 185 unrelated Brazilian patients with autosomal recessive nonsyndromic sensorineural hearing loss (43 heterozygous patients and 142 without any pathogenic mutation in the GJB2-coding region). We have found two patients (4.6%) carrying the IVS 1+1 G>A mutation in compound heterozygous with c.35delG mutation.

Prevalence of DFNB1 mutations in Argentinean children with non-syndromic deafness. Report of a novel mutation in GJB2

“…This mutation, which had not been previously studied in an Argentinean population, was found in 3% of pathogenic alleles. This frequency is similar to the recently described in Brazilian population [40]. Hence, we consider the study of IVS1 + 1G !…”

GJB2 Gene Testing, Etiologic Diagnosis and Genetic Counseling in Romanian Persons With Prelingual Hearing Loss

“…The allele frequency was found between 1% and 9.4% for GJB2 mutations among the Asian and Brazilian populations [21][22][23] and much higher in the Hungarian and Czech populations, around 23.4% and 45%, respectively [24,25]. This mutation is predicted to disrupt splicing, yielding no detectable mRNA [26] and is consistent with our data given that both patients presented profound bilateral hearing impairment.…”

Prevalence of IVS1+1G>A mutation among Iranian Azeri Turkish patients with autosomal recessive non-syndromic hearing loss (ARNSHL)

“…Searching neighboring gene GJB6 for common deletion (del(GJB6-D13S1830)) was negative for this mutation in the cohort studied [7]. Therefore, there may be mutations in other region of the GJB2 gene or other unidentified gene(s) responsible for ARNSHL [13]. The splice site mutation IVS1+1G>A, also called -3172G>A, in the splice donor site of intron 1 in GJB2 was originally considered by Denoyelle et al (1999) as a disruptive mutation yielding no detectable mRNA [13].…”

“…Therefore, there may be mutations in other region of the GJB2 gene or other unidentified gene(s) responsible for ARNSHL [13]. The splice site mutation IVS1+1G>A, also called -3172G>A, in the splice donor site of intron 1 in GJB2 was originally considered by Denoyelle et al (1999) as a disruptive mutation yielding no detectable mRNA [13]. Objective: Mutations in the GJB2 gene has been reported as a main cause for autosomal recessive nonsyndromic hearing loss (ARNSHL) all over the world.…”

“…In recent years IVS1+1G>A mutation have been investigated all over the world by genetic laboratories and this splice site have been found in several populations [3,5,9,[13][14][15][16][17][18][19].…”