Dataset Information

A novel pathogenic variant in the LRTOMT gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

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.

SUBMITTER: Sarmadi A

PROVIDER: S-EPMC7285524 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A novel pathogenic variant in the LRTOMT gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

Sarmadi Akram A Nasrniya Samane S Soleimani Farsani Maryam M Narrei Sina S Nouri Zahra Z Sepehrnejad Mahsa M Nilforoush Mohammad Hussein MH Abtahi Hamidreza H Tabatabaiefar Mohammad Amin MA

BMC medical genetics 20200609 1

<h4>Background</h4>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.<h4>Methods</h4>A proband from an Iranian consanguineous family was examined via WES, following ...[more]

PMID: 32517708

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Project description:The frequency of inherited bilateral autosomal recessive non-syndromic hearing loss (ARNSHL) in Pakistan is 1.6/1000 individuals. More than 50% of the families carry mutations in GJB2 while mutations in MYO15A account for about 5% of recessive deafness. In the present study a cohort of 30 ARNSHL families was initially screened for mutations in GJB2 and MYO15A. Homozygosity mapping was performed by employing whole genome single nucleotide polymorphism (SNP) genotyping in the families that did not carry mutations in GJB2 or MYO15A. Mutation analysis was performed for the known ARNSHL genes present in the homozygous regions to determine the causative mutations. This allowed the identification of a causative mutation in all the 30 families including 9 novel mutations, which were identified in 9 different families (GJB2 (c.598G>A, p.Gly200Arg); MYO15A (c.9948G>A, p.Gln3316Gln; c.3866+1G>A; c.8767C>T, p.Arg2923* and c.8222T>C, p.Phe2741Ser), TMC1 (c.362+18A>G), BSND (c.97G>C, p.Val33Leu), TMPRSS3 (c.726C>G, p.Cys242Trp) and MSRB3 (c.20T>G, p.Leu7Arg)). Furthermore, 12 recurrent mutations were detected in 21 other families. The 21 identified mutations included 10 (48%) missense changes, 4 (19%) nonsense mutations, 3 (14%) intronic mutations, 2 (9%) splice site mutations and 2 (9%) frameshift mutations. GJB2 accounted for 53% of the families, while mutations in MYO15A were the second most frequent (13%) cause of ARNSHL in these 30 families. The identification of novel as well as recurrent mutations in the present study increases the spectrum of mutations in known deafness genes which could lead to the identification of novel founder mutations and population specific mutated deafness genes causative of ARNSHL. These results provide detailed genetic information that has potential diagnostic implication in the establishment of cost-efficient allele-specific analysis of frequently occurring variants in combination with other reported mutations in Pakistani populations.

Dataset Information

A novel pathogenic variant in the LRTOMT gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

Publications

A novel pathogenic variant in the LRTOMT gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

Similar Datasets

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