Whole Exome Sequencing Identified a Novel Mutation in the LOXHD1 Gene in Consanguineous Iranian Families With Hearing Loss

Abstract

Background

Hearing loss is one of the most common sensory disorders caused by genetic and environmental factors. Autosomal recessive non-syndromic hearing loss (ARNSHL) is extremely heterogeneous, with over 100 genes known to be involved. Hearing loss can result from mutations in the LOXHD1 gene, which codes a highly conserved protein known as lipoxygenase and is located at 18q21.1. Despite the association between LOXHD1 mutations and ARNSHL, there are still few documented cases.

Methods

We examined a case of non-syndromic hearing loss in an Iranian family with a history of consanguinity and several affected siblings. Next-generation sequencing (NGS) was conducted on the proband to discover causal genetic alterations. Sanger sequencing was employed to confirm the identified variation.

Results

A novel likely pathogenic variant in the LOXHD1 gene, c.3713dupA (p.Asp1238Glufs*10), was identified. Sanger sequencing was used to confirm that the affected family members had this frameshift mutation.

Conclusion

Our findings broaden the mutational range of LOXHD1 linked to ARNSHL. This unique variant enhances the comprehension of the genetic underpinnings of hearing loss and may aid in molecular diagnostics and genetic counseling for impacted families.