Prevalence of two mutations p.V239D and p.Q446R of slc26a4 gene in hearing impaired individuals in Khyber Pakhtunkhwa, Pakistan

Abstract

Deafness is the most prevalent sensory disorder affecting 1-3.47 in 1000 live births. Approximately 15% of world’s population are affected by some degree of hearing loss, in which 17% have severe hearing impairment. Genetic hearing loss accounts for 50% of hearing loss from which 70% are from recessive trait in non-syndromic hearing loss (NSHL). Earlier epidemiological studies indicated mutations in SLC26A4 gene is one of the predominantly genes involved in ARNSHL is associated with enlarged vestibular aqueduct (EVA). The autosomal recessive non-syndromic hearing loss (ARNSHL) is associated with mutations in solute carrier family 26, member 4 (A4) gene which is the among most common known causes of ARNSHL worldwide. Over 200 mutations have been identified in SLC26A4 gene. Different regions and countries have identified specific variants of SLC26A4 gene, among which p.V239D and p.Q446R are more frequent mutation in Pakistani population. Studies have showed difference of frequency distribution of SLC26A4 linked to hearing loss among different ethnicities of Pakistan. This study is aimed to determine the frequency of two variants p.V239D and p.Q446R in SLC26A4 gene. All individuals voluntarily participated in the study, after informed consent from patients or their guardians, it was managed to collect a total of 26 peripheral blood samples from Pakistani population. DNA was extracted from these samples followed by DNA quantification and quality assessment. Tetra-primer Amplification Refractory Mutation System (T-ARMS) PCR was applied on 26 samples. All findings were compared with normal individuals control. Interestingly, these two mutations were not found in our study samples. Further studies are needed to gain insight of this gene11tic mechanisms for which large sample size from different ethnic groups of Pakistan is crucial. It will be very beneficial to analyze variants of SLC26A4 and other genes responsible for hearing loss. This is an important key for determining therapies in the future.