Spectrum and frequencies of mutations in the GJB2 (Cx26) gene among 156 Czech patients with pre‐lingual deafness

Abstract

Mutations in the gene gap junction beta 2 (GJB2), the gene for the connexin 26, are the most common cause of pre-lingual deafness worldwide. The mutation 35delG within GJB2 is prevalent in Europe. To date, there are no data about GJB2 mutation spectrum and frequencies from the Czech population. We investigated and report here the spectrum and frequencies of mutations in the GJB2 gene among 156 unrelated, congenital deafness Czech patients. Allele-specific polymerase chain reaction, together with fluorescent fragment analysis, were used for the detection of the 35delG mutation. The entire coding region of the GJB2 was directly sequenced in all patients who were not homozygous for the 35delG. No pathogenic mutation was detected in 51.9% of patients. At least one pathogenic mutation was found in 48.1% of patients, and both pathogenic mutations were detected in 37.8% of patients. Single mutations in a heterozygous state were detected in 10.3% of patients. The mutation 35delG accounts for 82.8% of detected disease mutations, Trp24stop accounts for 9.7% of pathogenic alleles and was found in patients with gypsy heritage. Mutation 313del14 accounts for 3.7% of pathogenic alleles. The frequency of 35delG heterozygotes in the Czech Republic is 1 : 29.6. Testing for only the three most common mutations would detect over 96% of all pathogenic alleles in the Czech Republic.

High prevalence of the W24X mutation in the gene encoding connexin‐26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non‐syndromic hearing loss

“…The finding of a high prevalence of the W24X mutation in Slovak and Spanish gypsies and in India traces the origins of the mutation to the Indian subcontinent and suggests that this GJB2 mutant allele may be the commonest in other European Romani populations. In fact, W24X has been reported in Czech gypsies [Seeman et al, 2004], and, without any indication of ethnicity, in Turkey [Uyguner et al, 2003], Hungary [Toth et al, 2004], Austria [Frei et al, 2002], Greece [Pampanos et al, 2002], and France [Roux et al, 2004], countries which have significant Romani minorities. In this work, we have found five different haplotypes associated with the W24X mutation, all of them sharing the same allele from marker D13S141, and 90% sharing also the same allele from marker (TG) n , suggesting that a founder effect for this mutation is responsible for its high prevalence among Spanish gypsies.…”

Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

“…Because congenital deafness is relatively common, affecting 1 of 2,000 newborns [20], and more than 50 different genes have been found to be involved [30], the origin of hearing loss in this case may be on account of mutations in other deafness genes and the association with CH may be coincidental. For this reason we additionally tested this patient for mutations in the GJB2/connexin26 gene, which is the most common cause of congenital sensorineural deafness [28], but did not find any mutations.…”

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

“…This is a much lower frequency when compared to GJB2 mutations, which could be up to 42.4%, in an analogous group of Czech patients (Seeman et al, 2004. SLC26A4 was tested in several populations (France, Holland, Germany, Spain, UK, USA, China and Japan).…”

“…The majority of cases are expected to be of genetic origin with significant dominance of autosomal recessive (AR) inheritance (up to 75%) and non-syndromic phenotype (Schrijver, 2004). The most important role in non-syndromic hearing loss (NSHL) is played by biallelic mutations in the GJB2 gene (Snoeckx et al, 2005), being responsible for almost 40% of early NSHL cases in the Czech population (Seeman et al, 2004Seeman & Sakmaryova, 2006).…”