The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families

Ghalia Al-Kasbi, Fathiya Al-Murshedi, Adila Al-Kindi, Nadia Al-Hashimi, Khalid Al-Thihli, Abeer Al-Saegh, Amna Al-Futaisi, Watfa Al-Mamari, Abdullah Al-Asmi, Zandre Bruwer, Khalsa Al-Kharusi, Samiya Al-Rashdi, Fahad Zadjali, Said Al-Yahyaee, Almundher Al-Maawali

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6 Citations (Scopus)


Global Developmental Delay/Intellectual disability (ID) is the term used to describe various disorders caused by abnormal brain development and characterized by impairments in cognition, communication, behavior, or motor skills. In the past few years, whole-exome sequencing (WES) has been proven to be a powerful, robust, and scalable approach for candidate gene discoveries in consanguineous populations. In this study, we recruited 215 patients affected with ID from 118 Middle Eastern families. Whole-exome sequencing was completed for 188 individuals. The average age at which WES was completed was 8.5 years. Pathogenic or likely pathogenic variants were detected in 32/118 families (27%). Variants of uncertain significance were seen in 33/118 families (28%). The candidate genes with a possible association with ID were detected in 32/118 (27%) with a total number of 64 affected individuals. These genes are novel, were previously reported in a single family, or cause strikingly different phenotypes with a different mode of inheritance. These genes included: AATK, AP1G2, CAMSAP1, CCDC9B, CNTROB, DNAH14, DNAJB4, DRG1, DTNBP1, EDRF1, EEF1D, EXOC8, EXOSC4, FARSB, FBXO22, FILIP1, INPP4A, P2RX7, PRDM13, PTRHD1, SCN10A, SCYL2, SMG8, SUPV3L1, TACC2, THUMPD1, XPR1, ZFYVE28. During the 5 years of the study and through gene matching databases, several of these genes have now been confirmed as causative of ID. In conclusion, understanding the causes of ID will help understand biological mechanisms, provide precise counseling for affected families, and aid in primary prevention.

Original languageEnglish
Article number18862
Pages (from-to)18862
JournalScientific Reports
Issue number1
Publication statusPublished - Nov 7 2022


  • Humans
  • Intellectual Disability/diagnosis
  • Pedigree
  • Whole Exome Sequencing
  • Genes, Recessive
  • Phenotype
  • Mutation
  • Peptide Elongation Factor 1/genetics
  • Membrane Proteins/genetics
  • Adaptor Proteins, Signal Transducing/genetics
  • Receptors, Cytoplasmic and Nuclear/genetics
  • F-Box Proteins/genetics

ASJC Scopus subject areas

  • General

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