Dataset Information

Report of a Novel Splicing Mutation in the MYO15A Gene in a Patient With Sensorineural Hearing Loss and Spectrum of the MYO15A Mutations.

ABSTRACT: Introduction:Autosomal recessive non-syndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder with an approximate incidence of 1.4:1000 in neonates. Mutations in more than 60 genes including the MYO15A gene has been reported in patients affected with ARNSHL. In the present study, we report a novel MYO15A mutation identified by clinical exome sequencing and confirmed by Sanger sequencing in a consanguineous Iranian family with ARNSHL. Case presentation:A 22-year-old woman with congenital non-syndromic sensorineural hearing loss referred to our medical genetic center. Her parents were consanguineous with F?=?1/16 (first cousin), and clinical examination of the patient exclude dysmorphic features. Sanger sequencing of GJB2 and GJB6 genes, which are the most common causes of ARNSHL, was negative. Then she underwent clinical exome sequencing. Outcome:We found a novel homozygote variant (c.9611_9612+8delTGGTGAGCAT) in the MYO15A gene which creates a shift in the reading frame starting at codon 3204. This variant was confirmed by Sanger sequencing in the patient and also in her parents who were heterozygous. Discussion:The present results suggest that the homozygous MYO15A (c.9611_9612+8delTGGTGAGCAT) variant is a pathogenic mutation and to the best of our knowledge, this mutation has not been reported in any database.

SUBMITTER: Akbariazar E

PROVIDER: S-EPMC6757496 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Report of a Novel Splicing Mutation in the <i>MYO15A</i> Gene in a Patient With Sensorineural Hearing Loss and Spectrum of the <i>MYO15A</i> Mutations.

Akbariazar Elinaz E Vahabi Ali A Abdi Rad Isa I

Clinical medicine insights. Case reports 20190922

<h4>Introduction</h4>Autosomal recessive non-syndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder with an approximate incidence of 1.4:1000 in neonates. Mutations in more than 60 genes including the <i>MYO15A</i> gene has been reported in patients affected with ARNSHL. In the present study, we report a novel <i>MYO15A</i> mutation identified by clinical exome sequencing and confirmed by Sanger sequencing in a consanguineous Iranian family with ARNSHL.<h4>Case pre ...[more]

PMID: 31579092

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Project description:BackgroundTo date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL.MethodsSubjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling.ResultsPathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive.ConclusionsTECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

Dataset Information

Report of a Novel Splicing Mutation in the MYO15A Gene in a Patient With Sensorineural Hearing Loss and Spectrum of the MYO15A Mutations.

Publications

Report of a Novel Splicing Mutation in the <i>MYO15A</i> Gene in a Patient With Sensorineural Hearing Loss and Spectrum of the <i>MYO15A</i> Mutations.

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