Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Clinical and Genetic Profile of Children With Unexplained Intellectual Disability/Developmental Delay and Epilepsy Publisher Pubmed



Nouri N1 ; Bahreini A2, 3 ; Nasiri J4 ; Salehi M1, 5
Authors

Source: Epilepsy Research Published:2021


Abstract

Objective: This study was conducted to evaluate the validity of performing whole exome sequencing in children with unexplained intellectual disability (ID), developmental delay (DD), and epilepsy. Methods: We enrolled 61 Iranian children with unexplained DD/ID, and epilepsy with no etiologic diagnosis. 64 % of cases were male and 36 % were female, with a mean age of 6.2 years (range, 38 days to 15 years). Approximately 79 % of patients were born to consanguineous parents or had non-related parents from a highly inbred local region. Whole-exome sequencing analysis followed by Sanger sequencing was performed in all patients. Results: Pathogenic/likely pathogenic variants were identified in 59% (36/61) of patients, consisting of 26 novel and 14 known alterations. Variants of unknown significance were observed in 6.5 % (4/61) of patients. Variants in 28 genes have not been previously reported in Iranian patients with ID. Several additional phenotypes, mostly microcephaly, were common in 57.4 % of cases. Additionally, epilepsy was refractory in 40 % of patients. Three groups of brain anomalies consisting of brain dysgenesis, brain atrophy, and leukodystrophy were identified in our cohort. Mutations in genes implicated in cellular metabolic pathways were the most common, followed by ion channel/ion transporter and transcription pathways. Discussion: High-throughput DNA sequencing of the Iranian population with a high rate of parental consanguinity is a valuable strategy for identifying genetic etiology in children with unexplained ID/DD and epilepsy. Determining the genetic basis and most commonly involved pathways may help to identify novel genes and targeted antiepileptic treatments. © 2021 Elsevier B.V.
Related Docs
View other Related Docs
1. Proband-Only Exome Sequencing for Intellectual Disability in Iran: Diagnostic Yield and Genetic Insights, American Journal of Medical Genetics, Part A (2024)
2. 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)
3. 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)
Experts (# of related papers)
View all Related Experts
Mohammad Amin Tabatabaiefar (13)
Mohammad Hussein Nilforoush (2)
Other Related Docs
4. Autozygosity-Driven Genetic Diagnosis in Consanguineous Families From Italy and the Greater Middle East, Human Genetics (2020)
5. 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)
6. Identification of Novel Mutations in Tpk1 and Slc19a3 Genes in Families Exhibiting Thiamine Metabolism Dysfunction Syndrome, Heliyon (2024)
7. A Homozygous Nonsense Variant in Uvssa Causes Uv‑Sensitive Syndrome From Very Large Kindred: The First Report From Iran, Advanced Biomedical Research (2023)
8. Novel In-Frame Duplication Variant Characterization in Late Infantile Metachromatic Leukodystrophy Using Whole-Exome Sequencing and Molecular Dynamics Simulation, PLoS ONE (2023)
9. A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, BMC Medical Genetics (2020)
10. A Novel Pathologic Variant in Otof in an Iranian Family Segregating Hereditary Hearing Loss, Otolaryngology - Head and Neck Surgery (United States) (2018)
11. 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)
12. 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)
13. 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)
14. 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)
15. The Identification of Two Pathogenic Variants in a Family With Mild and Severe Forms of Developmental Delay, Journal of Human Genetics (2021)
16. 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)
17. A Novel Heterozygous Truncating Variant in the Ago1 Gene in an Iranian Family With Schizophrenia As an Unreported Symptom, Annals of Human Genetics (2023)
18. 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)
19. Autoimmune Manifestations Among 461 Patients With Monogenic Inborn Errors of Immunity, Pediatric Allergy and Immunology (2021)
20. Acer3-Related Leukoencephalopathy: Expanding the Clinical and Imaging Findings Spectrum Due to Novel Variants, Human Genomics (2021)