Spectrum and frequency of connexin 26 & connexin 30 gene mutations in patients with congenital hearing loss from Ladakh India

Abstract

Background

Congenital hearing loss refers to prenatal hearing impairment, which is the commonly shared problem among sensory disorders that ranges from slight to profound. In this study, we screened the involvement of connexin 26 & connexin 30 gene in congenital hearing loss patients from the Kargil district of Ladakh, India by target gene sequencing.

Materials and methods

The peripheral blood sample of the patients was collected followed by DNA extraction and PCR of the target gene of interest. The amplified target gene was then sequenced and analysed for any changes in nucleotide sequence.

Results

In this study, the connexin 26 & connexin 30 are the target gene that are associated with hearing loss and in this study, we found mutations in the connexin 26 gene and none of the mutations were found in the connexin 30 gene. The mutations found in the connexin 26 gene are “NM_004004:c.71G>A, “NM_004004:c.223C>T, “NM_004004:c230G>A, “NM_004004:c.380G>A, and “NM_004004:c.439G>A which change the amino acids to W24X, R75W, W77X, R127H, and E147K respectively and the frequency of the connexin 26 mutations in patients was 23% and the overall mutations in the cohort were 14.5%. This study found that “NM_004004:c.71G>A (W24X) nucleotide variant as common mutation. Both homozygous as well as heterozygous variants were found. R127H was the only mutation observed in control samples. A significant association was seen between connexin 26 gene mutations and familial history of congenital hearing loss and consanguinity with the p-value P<0.001.

Conclusion and significance

Although the etiology has been found to be multifactorial. However, the role of any nucleotide variant in the gene of interest needs to be thoroughly investigated to study the genetic etiology of the anomalies. The results of this study showed a positive association between congenital hearing loss and the connexin 26 gene. However, we did not find any role of the connexin 30 gene in congenital hearing loss.