WHEN SHOULD ONE LOOK FOR IVS1+1G>A SPLICE MUTATION IN PATIENTS WITH NONSYNDROMIC SENSORINEURAL HEARING LOSS?
Olga Shubina-Oleinik, Marina Siniauskaya, Elena Merkulava, Anastasia Levaya-Smaliak, Oleg Davydenko, Nina Danilenko
(Institute of Genetics and Cytology, National Academy of Sciences of Belarus., Minsk, Belarus)
JHS 2014; 4(2): OA24-29
The splice site nucleotide substitution IVS1+1G>A in the non-coding part of the GJB2 gene is one of the recessive pathogenic mutations causing nonsyndromic sensorineural hearing loss (NSHL). We present here the results of a study of IVS1+1G>A among Belarusian patients with NSHL as well as among Belarusian controls with normal hearing.
Material and Methods: The PCR-RFLP method was used for genotyping. All tested patients were subdivided into three groups: those who carried only one mutant allele of GJB2 exon 2 (group A, 28 patients), those with no mutation of GJB2 exon 2 (group B, 150 patients), and patients with two mutations previously detected in the second exon of GJB2 or with one mutation and a large GJB6 deletion ΔD13S1830 (group C, 223 patients). Also 300 Belarusian people with normal hearing were screened for IVS1+1G>A.
Results: We detected 7 patients with IVS1+1G>A mutation in the A group, which explained hearing loss in 25% of this deafness cohort. None of the B or C group patients carried the IVS1+1G>A mutation. We also did not find any IVS1+1G>A mutation carriers among the 300 Belarusian control people with normal hearing.
Conclusions: IVS1+1G>A is the third-most frequent mutation (after 35delG and 312del14) among Belarusian patients with NSHL; its rate is 1.8% for the patient cohort we studied and the population frequency is below 0.33%. We propose to include the IVS1+1G>A mutation into a laboratory screening protocol for those patients with NSHL that carry one mutant allele of GJB2 exon 2.
Keywords: GJB2, IVS1 + 1G > A, non-syndromic deafness