Identification a novel pathogenic LRTOMT mutation in Mauritanian families with nonsyndromic deafness

Abstract

Although recessive mutations in GJB2 are the common genetic etiology of sensorineural hearing impairment (SNHI), variants in LRTOMT gene were also identified, mostly in Middle East and North African populations. Methods: Using Sanger sequencing we screened the exon 7 of LRTOMT in a cohort of 128 unrelated Mauritanian children with congenital deafness. Results: One biallelic missense mutation, predicted as pathogenic (c.179T>C;p.Leu60Pro) was found at homozygous state in four independent families. This variant, not reported before, was predicted to have a deleterious effect by SIFT (score: 0.01) and a disease-causing effect by Mutation Taster (prob: 1). Exploration of the encoded protein 3D structure revealed a disruption of an organized α helix (in the normal protein structure) to a random conformation. Early fitting of a cochlear implant seemed to improve the auditory ability of the patient carrying the biallelic variant. Conclusion: Further screening using a panel of deafness genes should provide a more comprehensive view of the heterogeneity of deafness genes underlying hearing impairment in our population.