Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Molecular Diagnosis of Hereditary Neuropathies by Whole Exome Sequencing and Expanding the Phenotype Spectrum Publisher Pubmed



Taghizadeh S1, 2 ; Vazehan R3 ; Beheshtian M1, 3 ; Sadeghinia F1 ; Fattahi Z1, 3 ; Mohseni M1, 3 ; Arzhangi S1 ; Nafissi S4 ; Kariminejad A3 ; Najmabadi H1, 3 ; Kahrizi K1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  2. 2. Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  3. 3. Kariminejad - Najmabadi Pathology and Genetics Center, Tehran, Iran
  4. 4. Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Archives of Iranian Medicine Published:2020


Abstract

Background: Inherited peripheral neuropathies (IPNs) are a group of neuropathies affecting peripheral motor and sensory neurons. Charcot-Marie-Tooth (CMT) disease is the most common disease in this group. With recent advances in next-generation sequencing (NGS) technologies, more than 100 genes have been implicated for different types of CMT and other clinically and genetically inherited neuropathies. There are also a number of genes where neuropathy is a major feature of the disease such as spinocerebellar ataxia (SCA) and hereditary spastic paraplegia (HSP). We aimed to determine the genetic causes underlying IPNs in Iranian families. Methods: We performed whole exome sequencing (WES) for 58 PMP22 deletion-/duplication-negative unrelated Iranian patients with a spectrum of phenotypes and with a preliminary diagnosis of hereditary neuropathies. Results: Twenty-seven (46.6%) of the cases were genetically diagnosed with pathogenic or likely pathogenic variants. In this study, we identified genetically strong variants within genes not previously linked to any established disease phenotype in five (8.6%) patients. Conclusion: Our results highlight the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs. Moreover, functional analysis is required for novel and uncertain variants. © 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Related Docs
View other Related Docs
1. Alopecia Areata-Like Pattern of Baldness: The Most Recent Update and the Expansion of Novel Phenotype and Genotype in the Ctnnb1 Gene, Neurological Sciences (2023)
2. Iranome: A Catalog of Genomic Variations in the Iranian Population, Human Mutation (2019)
3. Bi-Allelic Loss of Function Variant in the Nrcam Gene Is Associated With Motor-Predominant Axonal Polyneuropathy; the Second Report, Molecular Genetics and Genomic Medicine (2023)
4. Novel Stag3 Variant Associated With Primary Ovarian Insufficiency and Non-Obstructive Azoospermia in an Iranian Consanguineous Family, Gene (2022)
5. Clinical Features and Genetic Characteristics of Xlid Patients With Kdm5c Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant, Molecular Genetics and Genomic Medicine (2025)
6. Broadening the Phenotype and Genotype Spectrum of Glycogen Storage Disease by Unraveling Novel Variants in an Iranian Patient Cohort, Biochemical Genetics (2024)
7. Genotypes of European and Iranian Patients With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips, Blood Advances (2021)
8. A Biallelic Loss-Of-Function Variant in Tmem147 Causes Profound Intellectual Disability and Spasticity, Neurogenetics (2023)
Experts (# of related papers)
View all Related Experts
Nima Parvaneh (6)
Arya Sotoudeh (5)
Other Related Docs
9. Genetic Change Investigation in Dock1 Gene in an Iranian Family With Sign and Symptoms of Temporomandibular Joint Disorder (Tmd), Clinical Oral Investigations (2024)
10. Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b), Orphanet Journal of Rare Diseases (2020)
11. Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type Vi and Fanconi−Bickel Syndrome, Frontiers in Genetics (2021)
12. Description of Clinical Features and Genetic Analysis of One Ultra-Rare (Spg64) and Two Common Forms (Spg5a and Spg15) of Hereditary Spastic Paraplegia Families, Journal of Neurogenetics (2021)
13. Clinical Application of Next Generation Sequencing for Mendelian Disease Diagnosis in the Iranian Population, npj Genomic Medicine (2024)
14. Novel Tecpr2 Variant in Two Cases of Hereditary Sensory and Autonomic Neuropathy Type 9: Insights From Genetic Characterization and Comprehensive Literature Review, BMC Neurology (2024)
15. Distinct Genetic Variation and Heterogeneity of the Iranian Population, PLoS Genetics (2019)
16. Expanding the Genetic Spectrum of Giant Axonal Neuropathy: Two Novel Variants in Iranian Families, Molecular Genetics and Genomic Medicine (2023)
17. Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy, Genes (2023)
18. Clinical and Molecular Assessment of a Spastic Ataxia 4 (Spax4) Patient With a Novel Variant in the Mtpap Gene, and a Systematic Review, Gene (2025)
19. Nemaline Myopathy: Reclassification of Previously Reported Variants According to Acmg Guidelines, and Report of Novel Genetic Variants, European Journal of Human Genetics (2023)
20. Co-Existence of Phenylketonuria Either With Maple Syrup Urine Disease or Sandhoff Disease in Two Patients From Iran: Emphasizing the Role of Consanguinity, Journal of Pediatric Endocrinology and Metabolism (2016)
21. Deep Geno- and Phenotyping in Two Consanguineous Families With Cmt2 Reveals Hadha As an Unusual Disease-Causing Gene and an Intronic Variant in Gdap1 As an Unusual Mutation, Journal of Neurology (2021)
22. Expanding the Clinical and Neuroimaging Features of Nkx6-2-Related Hereditary Spastic Ataxia Type 8, European Journal of Medical Genetics (2020)
23. Autozygosity Mapping of Methylmalonic Acidemia Associated Genes by Short Tandem Repeat Markers Facilitates the Identification of Five Novel Mutations in an Iranian Patient Cohort, Metabolic Brain Disease (2018)
24. Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis, Journal of Clinical Immunology (2018)
25. Description of Combined Arhsp/Jals Phenotype in Some Patients With Spg11 Mutations, Molecular Genetics and Genomic Medicine (2020)
26. Genetic Homogeneity of a Tdp1 Variant, C.1478A>G, As the Main Disease-Causing Variant of Spinocerebellar Ataxia With Axonal Neuropathy 1 (Scan1) in the Middle East: A Systematic Review, Pediatric Neurology (2025)
27. Extending and Outlining the Genotypic and Phenotypic Spectrum of Novel Mutations of Nalcn Gene in Ihprf1 Syndrome: Identifying Recurrent Urinary Tract Infection, Neurological Sciences (2023)
28. An Iranian Congenital Adrenal Hypoplasia Patient With Elevated Testosterone in Infancy Due to a Novel Pathogenic Frameshift Variant in Nr0b1, International Journal of Endocrinology (2021)
29. Whole-Transcriptome Sequencing–Based Concomitant Detection of Viral and Human Genetic Determinants of Cutaneous Lesions, JCI Insight (2022)
30. Crystallographic Modeling of the Pnpt1:C.1453A>G Variant As a Cause of Mitochondrial Dysfunction and Autosomal Recessive Deafness; Expanding the Neuroimaging and Clinical Features, Mitochondrion (2021)
31. Clinical and Molecular Findings of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay: An Iranian Case Series Expanding the Genetic and Neuroimaging Spectra, Cerebellum (2023)
32. A Novel Homozygous Variant (C.5876T > C: P. Leu1959pro) in Dysf Segregates With Limb-Girdle Muscular Dystrophy: A Case Report, BMC Musculoskeletal Disorders (2024)
33. Association of Tmprss2 Gene Polymorphisms With Covid-19 Severity and Mortality: A Case-Control Study With Computational Analyses, Applied Biochemistry and Biotechnology (2022)
34. Homozygous Mefv Gene Variant and Pyrin-Associated Autoinflammation With Neutrophilic Dermatosis: A Family With a Novel Autosomal Recessive Mode of Inheritance, JAMA Dermatology (2021)
35. Waardenburg Syndrome Type 2A in a Large Iranian Family With a Novel Mitf Gene Mutation, BMC Medical Genomics (2021)
36. A Novel Heterozygous Missense Myh7 Mutation Potentially Causes an Autosomal Dominant Form of Myosin Storage Myopathy With Dilated Cardiomyopathy, BMC Cardiovascular Disorders (2023)
37. Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort, Journal of Allergy and Clinical Immunology: In Practice (2019)
38. Mutation Spectra of the Itgb2 Gene in Iranian Families With Leukocyte Adhesion Deficiency Type 1, Human Immunology (2016)
39. Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity, Clinical Immunology (2024)
40. Mitochondrial Dna Copy Number As a Hidden Player in the Progression of Multiple Sclerosis: A Bidirectional Two-Sample Mendelian Randomization Study, Molecular Neurobiology (2025)
41. Cep104 Gene May Involve in the Pathogenesis of a New Developmental Disorder Other Than Joubert Syndrome, Molecular Biology Reports (2022)
42. The First Iranian Patient With You-Hoover-Fong Syndrome and a Review of the Literature on 27 Cases: Expanding the Genotypic and Phenotypic Spectrum, Neurological Sciences (2024)
43. Whole-Exome Sequencing Reveals a Novel Mutation of Flna Gene in an Iranian Family With Nonsyndromic Tetralogy of Fallot, Lab Medicine (2021)
44. Flt3l Governs the Development of Partially Overlapping Hematopoietic Lineages in Humans and Mice, Cell (2024)
45. Identification and Functional Characterization of Two Novel Srd5a2 Variants in Iranian Siblings With 5Α-Reductase Type 2 Deficiency: Expanding the Mutational Spectrum and Implications for Genetic Diagnosis, Human Gene (2025)
46. Novel Mutations in Tnfrsf7/Cd27: Clinical, Immunologic, and Genetic Characterization of Human Cd27 Deficiency, Journal of Allergy and Clinical Immunology (2015)
47. Identification of Eleven Different Mutations Including Six Novel, in the Arylsulfatase B Gene in Iranian Patients With Mucopolysaccharidosis Type Vi, Molecular Biology Reports (2019)
48. Mutational Spectrum and Clinical Symptoms of Iranian Patients With Charcot-Marie-Tooth Disease: A Study of 23 Patients, Journal of Iranian Medical Council (2023)
49. A Novel Autosomal Recessive Gjb2-Associated Disorder: Ichthyosis Follicularis, Bilateral Severe Sensorineural Hearing Loss, and Punctate Palmoplantar Keratoderma, Human Mutation (2019)
50. Linkage Study Revealed Complex Haplotypes in a Multifamily Due to Different Mutations in Capn3 Gene in an Iranian Ethnic Group, Journal of Molecular Neuroscience (2016)