Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
A Novel Missense Mutation in Gipc3 Causes Sensorineural Hearing Loss in an Iranian Family Revealed by Targeted Next-Generation Sequencing Publisher Pubmed



Asgharzade S1 ; Tabatabaiefar MA2, 3 ; Mohammadiasl J4 ; Chaleshtori MH1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  2. 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Medical Genetics, School of Medicine, AhvazJundishapurUniversity of Medical Sciences, Ahvaz, Iran

Source: International Journal of Pediatric Otorhinolaryngology Published:2018


Abstract

Background: Recent studies have confirmed the utility of targeted next-generation sequencing (NGS), providing a remarkable opportunity to find variants in known disease genes, especially in genetically heterogeneous disorders such as hearing loss (HL). Methods: After excluding mutations in the most common autosomal recessive non-syndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis, we performed NGS in the proband an Iranian family with ARNSHL. The NimbleGen sequence capture array captures codingsequences (CDSs) and 100 bp of the flanking sequence of 129 common deafness genes (cat# Oto-DA3). NGSwas performed on the IlluminaHiSeq2000. BWA, SAMtools, Picard, GATK, Variant Tools, ANNOVAR, and IGV were applied for Bioinformatics analyses. Data filtering with allele frequencies (<5% in the 1000 Genomes Project and 5400 NHLBI exomes) and PolyPhen2/SIFTscores (>0.95) prioritized 1indel (insertions/deletions) and 3 missense variants in this family. Eventually, Sanger sequencing, segregation pattern, the frequency in 50 healthy matched normal controls, and evolutionary conservation of amino acid residues revealed the pathogenic variant. Results: We identified a novel missenseGIPC3 mutation, c.472G > A (p.Glu158 Lys). The pathogenicity of GIPC3c.472G > A was supported by its absence in the population databases and the healthy-matched controls.Sanger sequencing confirmed co-segregation of the mutation with HL. Conclusions: This study is the first report of the contribution of theGIPC3 gene to HL in the Iranian population.Targeted NGS allows easier detection of mutations in relatively uncommon deafness genes in families with ARNSHL. © 2018 Elsevier B.V.
Related Docs
View other Related Docs
1. Whole Exome Sequencing Identifies Novel Compound Heterozygous Pathogenic Variants in the Myo15a Gene Leading to Autosomal Recessive Non-Syndromic Hearing Loss, Molecular Biology Reports (2020)
2. A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, BMC Medical Genetics (2020)
3. Whole-Exome Sequencing Identifies a Recurrent Small In-Frame Deletion in Myo15a Causing Autosomal Recessive Nonsyndromic Hearing Loss in 3 Iranian Pedigrees, Lab Medicine (2022)
4. A Novel Tecta Mutation Causes Arnshl, International Journal of Pediatric Otorhinolaryngology (2017)
5. Molecular Diagnosis of Slc26a4-Related Hereditary Hearing Loss in a Group of Patients From Two Provinces of Iran, Intractable and Rare Diseases Research (2021)
6. A Novel Pathogenic Variant in the Marveld2 Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, Genomics (2019)
7. Next-Generation Sequencing Reveals a Novel Pathological Mutation in the Tmc1 Gene Causing Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Kindred, International Journal of Pediatric Otorhinolaryngology (2019)
8. Identification and Clinical Implications of a Novel Myo15a Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing, Audiology and Neurotology (2019)
Experts (# of related papers)
View all Related Experts
Mohammad Amin Tabatabaiefar (47)
Sayed Hamidreza Abtahi (4)
Other Related Docs
9. Screening of Myo7a Mutations in Iranian Patients With Autosomal Recessive Hearing Loss From West of Iran, Iranian Journal of Public Health (2017)
10. Gjb2 Mutations Causing Autosomal Recessive Non-Syndromic Hearing Loss (Arnshl) in Two Iranian Populations: Report of Two Novel Variants, International Journal of Pediatric Otorhinolaryngology (2018)
11. A Novel Pathologic Variant in Otof in an Iranian Family Segregating Hereditary Hearing Loss, Otolaryngology - Head and Neck Surgery (United States) (2018)
12. Mutation in Second Exon of Myo15a Gene Cause of Nonsyndromic Hearing Loss and Its Association in the Arab Population in Iran, Genetika (2016)
13. A Novel Cadherin 23 Variant for Hereditary Hearing Loss Reveals Additional Support for a Dfnb12 Nonsyndromic Phenotype of Cdh23, Audiology and Neurotology (2020)
14. The Role and Spectrum of Slc26a4 Mutations in Iranian Patients With Autosomal Recessive Hereditary Deafness, International Journal of Audiology (2015)
15. A Novel Pathogenic Variant in the Cabp2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family, Audiology and Neurotology (2019)
16. A New Compound Heterozygous Mutation in Gjb2 Causes Nonsyndromic Hearing Loss in a Consanguineous Iranian Family, International Journal of Pediatric Otorhinolaryngology (2015)
17. Mutation Analysis of Gjb2 and Gjb6 Genes and Screening of Nine Common Dfnb Loci in Iranian Pedigrees With Autosomal Recessive Nonsyndromic Hearing Loss, Indian Journal of Otology (2019)
18. A Novel Variant of Slc26a4 and First Report of the C.716T>A Variant in Iranian Pedigrees With Non-Syndromic Sensorineural Hearing Loss, American Journal of Otolaryngology - Head and Neck Medicine and Surgery (2018)
19. Identification of Novel Likely Pathogenic Variant in Cdh23 Causing Non-Syndromic Hearing Loss, and a Novel Variant in Otogl in an Extended Iranian Family, Egyptian Journal of Medical Human Genetics (2024)
20. Genetic Linkage Analysis of the Dfnb63 Locus in Families With Autosomal Recessive Nonsyndromic Hearing Loss From Hamadan and Kohgiluyeh and Boyer-Ahmad Provinces, Iran, Journal of Isfahan Medical School (2015)
21. A Pathogenic Variant in Slc26a4 Is Associated With Pendred Syndrome in a Consanguineous Iranian Family, International Journal of Audiology (2019)
22. Mutations in Gjb2 As Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of C.299-300Delat Mutation in Kurdish Population of Iran, Journal of Audiology and Otology (2019)
23. Screening of Dfnb3 in Iranian Families With Autosomal Recessive Non-Syndromic Hearing Loss Reveals a Novel Pathogenic Mutation in the Myth4 Domain of the Myo15a Gene in a Linked Family, Iranian Journal of Basic Medical Sciences (2016)
24. Screening of 10 Dfnb Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for Gjb2 Mutations, Iranian Journal of Public Health (2019)
25. Genetic Linkage Analysis of Dfnb40 and Dfnb48 Loci in Families With Autosomal Recessive Non-Syndromic Hearing Loss (Arnshl) From Western Provinces of Iran, Journal of Isfahan Medical School (2016)
26. Targeted Next-Generation Sequencing of a Deafness Gene Panel (Miamiotogenes) Analysis in Families Unsuitable for Linkage Analysis, BioMed Research International (2018)
27. Genetic Variant Effect Prediction by Supervised Nonnegative Matrix Tri-Factorization, Molecular Omics (2021)
28. Clinical Characterizations and Molecular Genetic Study of Two Co-Segregating Variants in Pdzd7 and Pde6c Genes Leading Simultaneously to Non-Syndromic Hearing Loss and Achromatopsia, BMC Medical Genomics (2024)
29. Next-Generation Sequencing Reveals a Novel Pathogenic Variant in the Atm Gene, International Journal of Neuroscience (2022)
30. Predicting Deleterious Missense Genetic Variants Via Integrative Supervised Nonnegative Matrix Tri-Factorization, Scientific Reports (2021)
31. Genetics of Hereditary Hearing Loss in East Iran Population: A Systematic Review of Gjb2 Mutations, Intractable and Rare Diseases Research (2019)
32. Genetics of Hearing Loss in North Iran Population: An Update of Spectrum and Frequency of Gjb2 Mutations, Journal of Audiology and Otology (2019)
33. Gjb2-Related Hearing Loss in Central Iran: Review of the Spectrum and Frequency of Gene Mutations, Annals of Human Genetics (2020)
34. The Study of Mutation in Lasr and Pqsr Genes in Extremely Drug Resistant and Multidrug Resistant Strains of Pseudomonas Aeruginosa From Burn Wound Infection, Jundishapur Journal of Microbiology (2019)
35. A Novel Carcinogenic Pi3kα Mutation Suggesting the Role of Helical Domain in Transmitting Nsh2 Regulatory Signals to Kinase Domain, Life Sciences (2021)
36. Mutation Spectrum of Autosomal Recessive Non-Syndromic Hearing Loss in Central Iran, International Journal of Pediatric Otorhinolaryngology (2015)
37. Targeted Sequencing of Cdh23 and Gjb2 Genes in an Iranian Pedigree With Usher Syndrome and Non-Syndromic Hearing Loss, Gene Reports (2021)
38. A Novel Mutation in Gjc2 Associated With Hypomyelinating Leukodystrophy Type 2 Disorder, Genomics and Informatics (2022)
39. Autozygosity-Driven Genetic Diagnosis in Consanguineous Families From Italy and the Greater Middle East, Human Genetics (2020)
40. Proband-Only Exome Sequencing for Intellectual Disability in Iran: Diagnostic Yield and Genetic Insights, American Journal of Medical Genetics, Part A (2024)
41. A Novel Pathogenic Variant in the Fzd6 Gene Causes Recessive Nail Dysplasia in a Large Iranian Kindred, Journal of Dermatological Science (2017)
42. A Novel Pathogenic Variant in Naglu (N-Acetyl-Alpha-Glucosaminidase) Gene Identified by Targeted Next-Generation Sequencing Followed by in Silico Analysis, Iranian Journal of Child Neurology (2019)
43. Understanding the Impact of Dis3 Cancer-Associated Mutations by in Silico Structure Modeling, Gene Reports (2020)
44. Use of in Silico Tools for Classification of Novel Missense Mutations Identified in Dystrophin Gene in Developing Countries, Gene (2014)
45. Using in Silico Bioinformatics Algorithms for the Accurate Prediction of the Impact of Spike Protein Mutations on the Pathogenicity, Stability, and Functionality of the Sars-Cov-2 Virus and Analysis of Potential Therapeutic Targets, Biochemical Genetics (2023)
46. A Novel Heterozygous Truncating Variant in the Ago1 Gene in an Iranian Family With Schizophrenia As an Unreported Symptom, Annals of Human Genetics (2023)
47. The Bioinformatics Report of Mutation Outcome on Nadph Flavin Oxidoreductase Protein Sequence in Clinical Isolates of H. Pylori, Current Microbiology (2016)
48. A Novel Mettl5 Variant Disrupting a Donor Splice Site Leads to Primary Microcephaly-Related Intellectual Disability in an Iranian Family: Clinical Features and Literature Review, Journal of Genetics (2023)
49. A Novel Mutation in the Pax3 Gene Causes Waardenburg Syndrome Type I in an Iranian Family, International Journal of Pediatric Otorhinolaryngology (2015)
50. The Identification of Two Pathogenic Variants in a Family With Mild and Severe Forms of Developmental Delay, Journal of Human Genetics (2021)