High prevalence in the Greek population of the 35delG mutation in the connexin 26 gene causing prelingual deafness

To the Editor: Mutations in the gene encoding the gap-junction protein connexin 26 (Cx26) on chromosome 13q11 were shown to be major contributors to prelingual, non-syndromic recessive deafness in Caucasian populations (1). One specific mutation, a deletion of G in a sequence of six Gs (35delG), has accounted for the majority of the mutations detected in the Cx26 gene and is one of the most frequent disease mutations identified so far (2–4). The high prevalence of prelingual, recessive deafness suggests that many people in the general population are symptom-free carriers of Cx26 mutations (3–7) and carrier frequencies of mutation 35delG of 1 in 25 and 1 in 42 were detected in Italian and Spanish people, respectively (4). The 35delG mutation was found to occur on different haplotypes, rather than being a founder mutation (7). It is possible that the stretch of six Gs constitutes a mutational hot spot due to polymerase slippage, since an insertion of G has also been detected (4). In order to estimate the 35delG carrier frequency in the Greek population, we analysed 395 voluntary, healthy Greek blood donors, originating from different parts of the country. The mean age was 30.8 years (range, 18–60 years). We used either allele-specific polymerase chain reaction (PCR) amplification of genomic DNA with primers, as previously published for the detection of the 35delG mutation (6), or allele-specific oligonucleotide (ASO) hybridization after PCR amplification (8). We further developed the allele-specific PCR by co-amplification of Cx26 with a segment of the X–Y homologous gene amelogenin (9), serving as an internal reaction control. We detected 14 heterozygotes, which gives a carrier frequency of 3.5%, or 1 in 28, in the Greek population [95% confidence interval (CI) 1 in 19 to 1 in 58]. In the Greek population, the 35delG mutation is thus more frequent than the predominant DF508 mutation in the cystic fibrosis transmembrane conductance regulator gene (about 2.3% carrier frequency) (10) and as frequent as the most common b-globin gene mutation (IVS1-110 G\A) causing b thalassemia (11). With an incidence of prelingual deafness of about 1 in 1000 children, homozygosity for the 35delG mutation should account for about 30% of all cases. A comparison with other studied populations is shown in Table 1. The highest 35delG carrier frequency found so far is in Italians and Greeks and this mutation might be particularly frequent in Mediterranean populations, but numbers of individuals analysed in some of the other studies are small. Other populations need to be studied in order to determine the precise distribution of this frequent point mutation. Until recently, deafness was thought to be a highly complex problem because of unparalleled genetic heterogeneity. This complexity has now been greatly reduced since the description of a very common mutation in the most common form of genetic hearing loss, which should enable easy DNA diagnosis, carrier detection and prenatal diagnosis in a high proportion of cases. Thalia Antoniadi Raquel Rabionet Christos Kroupis George A Aperis John Economides Jacob Petmezakis Effrosini Economou-Petersen Xa6ier Esti6ill Michael B Petersen Table 1. Connexin 26 35delG mutation carrier frequency in different populations