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A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family Publisher Pubmed



Sarmadi A1, 2 ; Nasrniya S1 ; Soleimani Farsani M3 ; Narrei S2 ; Nouri Z4 ; Sepehrnejad M5 ; Nilforoush MH5 ; Abtahi H5 ; Tabatabaiefar MA1, 6, 7
Authors
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Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Genetics Department, Erythron Pathobiology and Genetics Lab, Isfahan, Iran
  3. 3. Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran
  4. 4. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Otolaryngology, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  7. 7. GenTArget Corp (GTAC), Deputy of Research and Technology, Isfahan University of Medical Sciences, Isfahan, Iran

Source: BMC Medical Genetics Published:2020


Abstract

Background: Hearing loss (HL) is the most common sensorineural disorder with high phenotypic and genotypic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) constitutes a major share of HL cases. In the present study, Whole exome sequencing (WES) was applied to investigate the underlying etiology of HL in an Iranian patient with ARNSHL. Methods: A proband from an Iranian consanguineous family was examined via WES, following GJB2 sequencing. WES was utilized to find possible genetic etiology of the disease. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Co-segregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: WES results showed a novel frameshift (16 bp deletion) variant (p.Ala170Alafs*20) in the LRTOMT gene. This variant, which resides in exon 6, was found to be co-segregating in the family. It fulfils the criteria set by the ACMG guidelines of being pathogenic. Conclusion: Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL, which is a genetically heterogeneous disorder, in a patient with ARNSHL. © 2020 The Author(s).
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