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Review
. 2024 Apr;28(8):e18119.
doi: 10.1111/jcmm.18119.

Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades

Madiha Shadab  1 , Ansar Ahmed Abbasi  1 , Ahsan Ejaz  2   3 , Afif Ben-Mahmoud  4 , Vijay Gupta  4 , Hyung-Goo Kim  4   5 , Barbara Vona  6   7
Affiliations
Review

Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades

Madiha Shadab et al. J Cell Mol Med. 2024 Apr.

Abstract

Hearing loss is a clinically and genetically heterogeneous disorder, with over 148 genes and 170 loci associated with its pathogenesis. The spectrum and frequency of causal variants vary across different genetic ancestries and are more prevalent in populations that practice consanguineous marriages. Pakistan has a rich history of autosomal recessive gene discovery related to non-syndromic hearing loss. Since the first linkage analysis with a Pakistani family that led to the mapping of the DFNB1 locus on chromosome 13, 51 genes associated with this disorder have been identified in this population. Among these, 13 of the most prevalent genes, namely CDH23, CIB2, CLDN14, GJB2, HGF, MARVELD2, MYO7A, MYO15A, MSRB3, OTOF, SLC26A4, TMC1 and TMPRSS3, account for more than half of all cases of profound hearing loss, while the prevalence of other genes is less than 2% individually. In this review, we discuss the most common autosomal recessive non-syndromic hearing loss genes in Pakistani individuals as well as the genetic mapping and sequencing approaches used to discover them. Furthermore, we identified enriched gene ontology terms and common pathways involved in these 51 autosomal recessive non-syndromic hearing loss genes to gain a better understanding of the underlying mechanisms. Establishing a molecular understanding of the disorder may aid in reducing its future prevalence by enabling timely diagnostics and genetic counselling, leading to more effective clinical management and treatments of hearing loss.

Keywords: Pakistani population; genetic counselling; genetic epidemiology; genotype; non‐syndromic hearing loss; phenotype.

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Conflict of interest statement

The authors confirm that there are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Timeline of 39 ARNSHL genes identified by collaborating with the Pakistani population over the past 25 years.
FIGURE 2
FIGURE 2
Pie chart showing the results of Metascape analysis of enriched gene ontology (GO) clusters. The chart displays the top 12 clusters and their representative enriched terms (one per cluster). The ‘Count’ refers to the number of genes in our list of 51 genes associated with ARNSHL that are included in the given ontology term. To classify the genes associated with ARNSHL according to their function, we performed pathway and process enrichment and network analysis using Metascape (http://metascape.org). Using this approach, we identified the enrichment of GO terms and genes related to various biological pathways.
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