Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Evaluation of Pathogenic Variant in Wfs1 in a Patient With Wolfram Syndrome Publisher



Hoseinzadeh M1, 2 ; Jahani MM2, 3 ; Nasrniya S1 ; Tabatabaiefar MA1, 2, 4, 5
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Research and Development, Harmonic Medical Genetics Lab, Isfahan, Iran
  3. 3. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Egyptian Journal of Medical Human Genetics Published:2025


Abstract

Objective: Wolfram syndrome (WS) is a genetically disorder that affect on many organs, and neurodegenerative disorder. Although various clinical dysfunctions may have different onset times, they can collectively contribute to delays in the diagnosis of the disorder. To date, more than 200 pathogenic and likely pathogenic variant have been identified. In the present investigation, we evaluated three families with WS and reported a mutation in the WFS1. Methods: This study, we have evaluated mutation in the WFS gene in three consanguineous families including three patients with a history of young-onset DM, progressive hearing loss and optic atrophy further neurological abnormalities. Results: Sequencing results showed a novel homozygous stop-gain variant, c.1444A > T (p.K482X), and two previously reported mutations (c.2006A > G and c.2105G > A) in exon 8 of WFS1 gene. The variant interpretation was done according to the genetic guidelines. Finally, p.K482X was determined as a novel pathogen variant. Also, analysis showed that variants in parents were heterozygous. Conclusions: The present survey, revealed a novel nonsense mutation in the wolframin protein, creates a frameshift which causes a premature stop codon truncating the protein in amino acid 482 residues. This mutation occurs in transmembrane domain and causes elimination of 46% of wolframin protein. © The Author(s) 2025.
Related Docs
View other Related Docs
1. Significant Expressivity of Wolfram Syndrome: Phenotypic Assessment of Two Known and One Novel Mutation in the Wfs1 Gene in Three Iranian Families, Molecular Biology Reports (2014)
2. Clinical and Molecular Assessment of 13 Iranian Families With Wolfram Syndrome, Endocrine (2019)
3. Homozygosity Mapping and Direct Sequencing Identify a Novel Pathogenic Variant in the Cisd2 Gene in an Iranian Wolfram Syndrome Family, Acta Diabetologica (2020)
4. Clinical and Genetic Analysis of Two Wolfram Syndrome Families With High Occurrence of Wolfram Syndrome and Diabetes Type Ii: A Case Report, BMC Medical Genetics (2020)
5. A Comprehensive Genetic and Clinical Evaluation of Waardenburg Syndrome Type Ii in a Set of Iranian Patients, International Journal of Molecular and Cellular Medicine (2018)
6. Sox10 Mutation Causes Waardenburg Syndrome Associated With Distinctive Phenotypic Features in an Iranian Family: A Clue for Phenotype-Directed Genetic Analysis, International Journal of Pediatric Otorhinolaryngology (2017)
7. A Novel Pathogenic Variant in the Mitf Gene Segregating With a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred, Molecular Syndromology (2017)
8. Molecular and Clinical Characterization of Waardenburg Syndrome Type I in an Iranian Cohort With Two Novel Pax3 Mutations, Gene (2015)
Experts (# of related papers)
View all Related Experts
Mohammad Amin Tabatabaiefar (31)
Sayed Hamidreza Abtahi (3)
Other Related Docs
9. A Novel Pathologic Variant in Otof in an Iranian Family Segregating Hereditary Hearing Loss, Otolaryngology - Head and Neck Surgery (United States) (2018)
10. A Novel Mutation in the Pax3 Gene Causes Waardenburg Syndrome Type I in an Iranian Family, International Journal of Pediatric Otorhinolaryngology (2015)
11. 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)
12. A Novel Cadherin 23 Variant for Hereditary Hearing Loss Reveals Additional Support for a Dfnb12 Nonsyndromic Phenotype of Cdh23, Audiology and Neurotology (2020)
13. A Novel Tecta Mutation Causes Arnshl, International Journal of Pediatric Otorhinolaryngology (2017)
14. 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)
15. A Novel Mutation in Gjc2 Associated With Hypomyelinating Leukodystrophy Type 2 Disorder, Genomics and Informatics (2022)
16. Targeted Next-Generation Sequencing of a Deafness Gene Panel (Miamiotogenes) Analysis in Families Unsuitable for Linkage Analysis, BioMed Research International (2018)
17. Targeted Sequencing of Cdh23 and Gjb2 Genes in an Iranian Pedigree With Usher Syndrome and Non-Syndromic Hearing Loss, Gene Reports (2021)
18. 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)
19. 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)
20. 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)
21. A New Compound Heterozygous Mutation in Gjb2 Causes Nonsyndromic Hearing Loss in a Consanguineous Iranian Family, International Journal of Pediatric Otorhinolaryngology (2015)
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. A Novel Missense Mutation in Gipc3 Causes Sensorineural Hearing Loss in an Iranian Family Revealed by Targeted Next-Generation Sequencing, International Journal of Pediatric Otorhinolaryngology (2018)
24. Molecular Diagnosis of Slc26a4-Related Hereditary Hearing Loss in a Group of Patients From Two Provinces of Iran, Intractable and Rare Diseases Research (2021)
25. Identification and Clinical Implications of a Novel Myo15a Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing, Audiology and Neurotology (2019)
26. Mutation in Second Exon of Myo15a Gene Cause of Nonsyndromic Hearing Loss and Its Association in the Arab Population in Iran, Genetika (2016)
27. 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)
28. 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)
29. A Novel Pathogenic Variant in the Cabp2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family, Audiology and Neurotology (2019)
30. 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)
31. A Novel Pathogenic Variant in the Marveld2 Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, Genomics (2019)
32. 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)
33. Screening of Myo7a Mutations in Iranian Patients With Autosomal Recessive Hearing Loss From West of Iran, Iranian Journal of Public Health (2017)
34. 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)
35. Two Novel Homozygous Rab3gap1 Mutations Cause Warburg Micro Syndrome, Human Genome Variation (2015)
36. A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, BMC Medical Genetics (2020)