Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Proband-Only Exome Sequencing for Intellectual Disability in Iran: Diagnostic Yield and Genetic Insights Publisher



Ghalamkari S1 ; Mianesaz H2 ; Chitsaz A3, 4 ; Ghazavi M5 ; Salehi M6
Authors
Show Affiliations
Authors Affiliations
  1. 1. Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  2. 2. Department of Human Genetics, Medical School, University of Debrecen, Debrecen, Hungary
  3. 3. Department of Neurology, Isfahan University of Medical Sciences Isfahan, Isfahan, Iran
  4. 4. Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Pediatrics, Isfahan University of Medical Science, Isfahan, Iran
  6. 6. Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Source: American Journal of Medical Genetics, Part A Published:2024


Abstract

Intellectual disability (ID) is a leading cause for referral to genetic services, with the most severe cases typically attributed to single genetic defects. This study aimed to evaluate the diagnostic yield of cost-effective proband-only exome sequencing for individuals diagnosed with ID within the Iranian population for the first time where a high rate of parental consanguinity exists. A total of 99 unrelated patients with ID were investigated by exome sequencing during 8 years. As a result, 43 pathogenic/likely pathogenic variants were identified in 40 patients, indicating a molecular diagnostic rate of 40.4% (40/99). The inclusion of five chromosomal copy number variations in the subsequent analysis increased the diagnostic rate of proband-only exome sequencing to 45.4% (45/99). Additionally, parental testing revealed five de novo variants. This contributed to a total diagnostic rate of 50.5% (50/99). In our study, proband-only exome sequencing achieved a remarkable diagnostic rate, identifying nearly half of the ID cases. This rate of diagnosis could be primarily attributed to prevalent consanguineous marriage in the Iranian population and the rare identification of de novo variants. With the ongoing advancements in neurogenetics, proband-only exome sequencing demonstrates significant potential as a future cost-effective diagnostic approach in Iran. © 2024 Wiley Periodicals LLC.
Related Docs
View other Related Docs
1. Clinical and Genetic Profile of Children With Unexplained Intellectual Disability/Developmental Delay and Epilepsy, Epilepsy Research (2021)
2. 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)
3. The Identification of Two Pathogenic Variants in a Family With Mild and Severe Forms of Developmental Delay, Journal of Human Genetics (2021)
4. Whole Exome Sequencing Revealed Variants in Four Genes Underlying X-Linked Intellectual Disability in Four Iranian Families: Novel Deleterious Variants and Clinical Features With the Review of Literature, BMC Medical Genomics (2023)
5. Molecular and Phenotypical Findings of a Novel De Novo Syngap1 Gene Variant in an 11-Year-Old Iranian Boy With Intellectual Disability, Lab Medicine (2024)
6. 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)
7. A Novel De Novo Frameshift Variant in the Chd2 Gene Related to Intellectual and Developmental Disability, Seizures and Speech Problems, Molecular Genetics and Genomic Medicine (2024)
8. A Novel Pathologic Variant in Otof in an Iranian Family Segregating Hereditary Hearing Loss, Otolaryngology - Head and Neck Surgery (United States) (2018)
Experts (# of related papers)
View all Related Experts
Mohammad Amin Tabatabaiefar (33)
Tooba Momen (4)
Other Related Docs
9. Autozygosity-Driven Genetic Diagnosis in Consanguineous Families From Italy and the Greater Middle East, Human Genetics (2020)
10. X-Linked Mental Retardation-Hypotonic Facies Syndrome: Exome Sequencing Identifies Novel Clinical Characteristics Associated With C.5182G>C Mutation in the Atrx Gene, Molecular Genetics and Genomic Medicine (2022)
11. Copy Number Analysis in a Large Cohort Suggestive of Inborn Errors of Immunity Indicates a Wide Spectrum of Relevant Chromosomal Losses and Gains, Journal of Clinical Immunology (2022)
12. Clinical, Immunologic, and Genetic Spectrum of 696 Patients With Combined Immunodeficiency, Journal of Allergy and Clinical Immunology (2018)
13. A Deleterious Frameshift Insertion Mutation in the Znf142 Gene Leads to Intellectual Developmental Disorder With Impaired Speech in Three Affected Siblings: Clinical Features and Literature Review, Molecular Genetics and Genomic Medicine (2023)
14. The First Report of a Patient With Trisomy 4P and Monosomy 10Q, Archives of Iranian Medicine (2019)
15. Comprehensive Review and Outline of Genotypes and Phenotypes of Arboleda-Tham Syndrome Spectrum: Insights From Novel Variants, Molecular Biology Reports (2025)
16. A Novel Homozygote Pathogenic Variant in the Diaph1 Gene Associated With Seizures, Cortical Blindness, and Microcephaly Syndrome (Scbms): Report of a Family and Literature Review, Molecular Genetics and Genomic Medicine (2024)
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. Two Distinct Deleterious Causative Variants in a Family With Multiple Cancer-Affected Patients, Advanced Biomedical Research (2023)
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. Consanguineous Marriages in the Genetic Counseling Centers of Isfahan and the Ethical Issues of Clinical Consultations, Journal of Medical Ethics and History of Medicine (2017)
21. Whole Exome Sequencing Revealed a Novel Gjb1 Pathogenic Variant and a Rare Bscl2 Mutation in Two Iranian Large Pedigrees With Multiple Affected Cases of Charcot-Marie-Tooth, International Journal of Molecular and Cellular Medicine (2019)
22. Using Whole Exome Sequencing in Determining the Genetic Cause of Parkinson Disease in an Iranian Family, Neurology Asia (2021)
23. A Homozygous Nonsense Variant in Uvssa Causes Uv‑Sensitive Syndrome From Very Large Kindred: The First Report From Iran, Advanced Biomedical Research (2023)
24. Genetic Polymorphism of 8 Y-Str Loci in Native Population of Isfahan Province in Central Part of Iran, Annals of Human Biology (2017)
25. A Novel Nr0b1 Mutation Correlated With X-Linked Adrenal Hypoplasia Congenital (Ahc), Gene Reports (2022)
26. Genetic Analysis of Mecp2 Gene in Iranian Patients With Rett Syndrome, Iranian Journal of Child Neurology (2019)
27. Novel In-Frame Duplication Variant Characterization in Late Infantile Metachromatic Leukodystrophy Using Whole-Exome Sequencing and Molecular Dynamics Simulation, PLoS ONE (2023)
28. Exome-First Approach Identified Novel Homozygous Dedicator of Cytokinesis 8 (Dock8) Mutations in Three Unrelated Iranian Pedigrees Suspected With Hyper-Ige Syndrome, Iranian Journal of Allergy, Asthma and Immunology (2020)
29. An Update of Spectrum and Frequency of Gjb2 Mutations Causing Hearing Loss in the South of Iran: A Literature Review, International Journal of Pediatric Otorhinolaryngology (2019)
30. Down Syndrome: Current Status, Challenges and Future Perspectives, International Journal of Molecular and Cellular Medicine (2016)
31. Genetic Mutations and Immunological Features of Severe Combined Immunodeficiency Patients in Iran, Immunology Letters (2019)
32. Genetic Polymorphisms of Y-Chromosome Short Tandem Repeats (Y-Strs) in a Male Population From Golestan Province, Iran, Molecular Biology Research Communications (2020)
33. A Novel Heterozygous Truncating Variant in the Ago1 Gene in an Iranian Family With Schizophrenia As an Unreported Symptom, Annals of Human Genetics (2023)
34. Targeted Next Generation Sequencing Reveals Genetic Defects Underlying Inherited Retinal Disease in Iranian Families, Molecular Vision (2019)
35. 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)
36. Association of Ahsg With Alopecia and Mental Retardation (Apmr) Syndrome, Human Genetics (2017)
37. Possible Dual Contribution of a Novel Gucy2d Mutation in the Development of Retinal Degeneration in a Consanguineous Population, European Journal of Medical Genetics (2020)
38. Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis, Journal of Clinical Immunology (2018)
39. 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)
40. Characterization of a Novel Androgen Receptor Gene Variant Identified in an Iranian Family With Complete Androgen Insensitivity Syndrome (Cais): A Molecular Dynamics Simulation Study, Journal of Biomolecular Structure and Dynamics (2023)
41. 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)
42. Clinical and Molecular Assessment of Iranian Families With Severe Congenital Neutropenia, Identification of Hyou1 and Shoc2 As Potential Novel Gene Defects, Iranian Journal of Allergy, Asthma and Immunology (2022)
43. A Novel Pathogenic Variant in the Cabp2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family, Audiology and Neurotology (2019)
44. 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)
45. A Novel Pathogenic Variant in the Marveld2 Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, Genomics (2019)
46. The Role and Spectrum of Slc26a4 Mutations in Iranian Patients With Autosomal Recessive Hereditary Deafness, International Journal of Audiology (2015)
47. Ataxia With Vitamin E Deficiency: Case Series, Vitamin E Therapy Response, Founder Effect, and in Silico Analysis, Clinical Genetics (2025)
48. Chromosomal Abnormalities in Regions 8Q22 and 13Q32 Associated With Different Disorders in an Iranian Family, Journal of Sciences, Islamic Republic of Iran (2012)
49. Identification of Novel Mutations in Tpk1 and Slc19a3 Genes in Families Exhibiting Thiamine Metabolism Dysfunction Syndrome, Heliyon (2024)
50. Next-Generation Sequencing Reveals a Novel Pathogenic Variant in the Atm Gene, International Journal of Neuroscience (2022)