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Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus
  1. Anas M Alazami1,
  2. Hadia Hijazi1,
  3. Mohammed S Al-Dosari1,2,
  4. Ranad Shaheen1,
  5. Amal Hashem3,
  6. Mohammed A Aldahmesh1,
  7. Jawahir Y Mohamed1,
  8. Amal Kentab4,
  9. Mustafa A Salih4,
  10. Ali Awaji5,
  11. Tariq A Masoodi6,
  12. Fowzan S Alkuraya1,4,7
  1. 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  2. 2Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
  3. 3Department of Pediatrics, Prince Sultan Military and Medical City, Riyadh, Saudi Arabia
  4. 4Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
  5. 5Department of Pediatrics, Jaizan Central Hospital, Jaizan, Saudi Arabia
  6. 6Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  7. 7Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Fowzan S Alkuraya, Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia; falkuraya{at}


Background Intellectual disability (ID) is one of the most common forms of disability worldwide, displaying a wide range of aetiologies and affecting nearly 2% of the global population.

Objective To describe a novel autosomal recessive form of ID with strabismus and its underlying aetiology.

Materials and methods Autozygosity mapping, linkage analysis and exome sequencing were performed in a large multiplex consanguineous family that segregates ID and strabismus. Exome sequencing was independently performed in three other consanguineous families segregating the same disease. Direct sequencing of the resulting candidate gene was performed in four additional families with the same phenotype.

Results A single missense mutation was identified in ADAT3 in all studied families on an ancient ancestral haplotype. This gene encodes one of two eukaryotic proteins that are necessary for the deamination of adenosine at position 34 to inosine in t-RNA. Our results show the first human mutation in the t-RNA editing machinery and expand the landscape of pathways involved in the pathogenesis of ID.

  • adenosine deaminase
  • RNA editing
  • intellectual disability
  • autozygome
  • exome

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