title: Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus.
abstract: 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.
  
  
  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.
authors.affiliation: Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Anas M
authors.initials: AM
authors.lastname: Alazami
authors.forename: Hadia
authors.initials: H
authors.lastname: Hijazi
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Dosari
authors.forename: Ranad
authors.initials: R
authors.lastname: Shaheen
authors.forename: Amal
authors.initials: A
authors.lastname: Hashem
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aldahmesh
authors.forename: Jawahir Y
authors.initials: JY
authors.lastname: Mohamed
authors.forename: Amal
authors.initials: A
authors.lastname: Kentab
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Salih
authors.forename: Ali
authors.initials: A
authors.lastname: Awaji
authors.forename: Tariq A
authors.initials: TA
authors.lastname: Masoodi
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015331:Cohort Studies; D003241:Consanguinity; D059472:Exome / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism; D013285:Strabismus / Q000235:genetics*
chemical_list: D012343:RNA, Transfer; D000243:Adenosine Deaminase
keywords: RNA editing; adenosine deaminase; autozygome; exome; intellectual disability