• A R Hamzeh, P Nair, M Mohamed, F Saif, N Tawfiq, M T Al-Ali, and F Bastaki.
• Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates. abdul.hamzeh@hmaward.org.ae.
• Ir J Med Sci. 2017 May 1; 186 (2): 333337333-337.

BackgroundIntellectual 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.AimsThe study sought to characterize two cases of ATR-X in a Yemeni family clinically and molecularly.MethodsPCR 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.ResultsMolecular 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.ConclusionsThe 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.

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