title: A novel missense mutation in ATRX uncovered in a Yemeni family leads to alpha-thalassemia/mental retardation syndrome without alpha-thalassemia.
abstract: BACKGROUND
  Intellectual disability (ID) features in numerous heritable medical conditions that result from ATRX mutations. Alpha-thalassemia mental retardation syndrome (ATR-X syndrome) is the most notable manifestation of ATRX dysfunction. In addition to ID, genitourinary and craniofacial abnormalities are regularly observed with or without alpha-thalassemia.
  
  
  OBJECTIVE
  The study sought to characterize two cases of ATR-X in a Yemeni family clinically and molecularly.
  
  
  METHODS
  PCR amplification and Sanger sequencing were used to study the ATRX gene in a Yemeni family. Also, methylation-sensitive PCR was used to perform X-inactivation studies. CADD, SNAP2 and PolyPhen-2 helped to predict the functional consequences of the variant.
  
  
  RESULTS
  Molecular testing revealed a novel hemizygous missense mutation (c.5666T>G) in the ATRX gene in the two Yemeni brothers. This mutation was found in a heterozygous state in the mother, with the chromosome harboring the mutated allele being under strongly skewed X-inactivation.
  
  
  CONCLUSIONS
  The mutated gene is predicted to have a disrupted SNF-2 domain at a conserved residue; p.Leu1889Trp, which is deemed functionally damaging. This report offers, for the first time, full clinical and molecular characterization of a novel ATRX variant in an Arab family.
authors: Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates. abdul.hamzeh@hmaward.org.ae.
authors: A R
authors: AR
authors: Hamzeh
authors: Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates.
authors: P
authors: P
authors: Nair
authors: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors: M
authors: M
authors: Mohamed
authors: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors: F
authors: F
authors: Saif
authors: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors: N
authors: N
authors: Tawfiq
authors: Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates.
authors: M T
authors: MT
authors: Al-Ali
authors: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors: F
authors: F
authors: Bastaki
mesh_terms: D000483:Alleles; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics*
keywords: ATRX; Chromatin remodelers; Novel mutation; X-linked mental retardation; Yemeni