• Anas M Alazami, Hadia Hijazi, Mohammed S Al-Dosari, Ranad Shaheen, Amal Hashem, Mohammed A Aldahmesh, Jawahir Y Mohamed, Amal Kentab, Mustafa A Salih, Ali Awaji, Tariq A Masoodi, and Fowzan S Alkuraya.
• Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia.
• J. Med. Genet. 2013 Jul 1; 50 (7): 425-30.

BackgroundIntellectual 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.ObjectiveTo describe a novel autosomal recessive form of ID with strabismus and its underlying aetiology.Materials And MethodsAutozygosity 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.ResultsA 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.

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