Spectrum of Genetic Changes in Patients with Non-Syndromic Hearing Impairment and Extremely High Carrier Frequency of 35delG GJB2 Mutation in Belarus

The genetic nature of sensorineural hearing loss (SNHL) has so far been studied for many ethnic groups in various parts of the world. The single-nucleotide guanine deletion (35delG) of the GJB2 gene coding for connexin 26 was shown to be the main genetic cause of autosomal recessive deafness among Europeans. Here we present the results of the first study of GJB2 and three mitochondrial mutations among two groups of Belarusian inhabitants: native people with normal hearing (757 persons) and 391 young patients with non-syndromic SNHL. We have found an extremely high carrier frequency of 35delG GJB2 mutation in Belarus −5.7%. This point deletion has also been detected in 53% of the patients with SNHL. The 312del14 GJB2 was the second most common mutation in the Belarus patient cohort. Mitochondrial A1555G mt-RNR1 substitution was found in two SNHL patients (0.55%) but none were found in the population cohort. No individuals carried the A7445G mutation of mitochondrial mt-TS1. G7444A as well as T961G substitutions were detected in mitochondrial mt-RNR1 at a rate of about 1% both in the patient and population cohorts. A possible reason for Belarusians having the highest mutation carrier frequency in Europe 35delG is discussed

Percentages of DD and NN <i>35delG</i> genotypes among Belarus SNHL patients with different degrees of hearing loss.

<p>Percentages of DD and NN <i>35delG</i> genotypes among Belarus SNHL patients with different degrees of hearing loss.</p

Map of Belarus.

<p>Figures indicate the regions where the population samples have been collected; the Polessie region is shown dashed.</p

Genotype/phenotype correlations for the patients with (D) and without (N) <i>35delG</i> mutation.

**<p>The difference of DD % with other patient groups is significant (P<0,02).</p

Primers, PCR conditions and endonucleases for genotyping.

<p>Notes</p>*<p>- self-designed primers;</p>**<p><b>-</b> for each sample without <i>XbaI</i> recognition site sequencing was carried out; Norm – normal, Mut – mutant alleles; the nucleotide positions and substitutions of mtDNA are given relative to the rCRS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036354#pone.0036354-Andrews1" target="_blank">[40]</a>.</p

Rates of mitochondrial mutations in the Belarus population and patient cohorts with SNHL.

<p>Rates of mitochondrial mutations in the Belarus population and patient cohorts with SNHL.</p

The rates of GJB2 and <i>del</i>(GJB6- D13S1830) mutations in Belarus SNHL patient cohort.

*<p>Degree of HL: mod – moderate; s – severe, pr – profound, x - no audiological data.</p

The rate of <i>35delG</i> heterozygotes in the population cohort (native inhabitants from six regions of Belarus).

**<p>The difference in rates between south-west and all the other regions is significant (P<0,02).</p