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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
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Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, United States
  3. 3. KaryoGen, Isfahan, Iran
  4. 4. Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

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.
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