A novel mutation in the last exon of ATRX in a patient with α‐thalassemia myelodysplastic syndrome

• Published in: European journal of haematology Vol. 76; no. 5; pp. 432 - 435
• Main Authors: Costa, Daniel B., Fisher, Christopher A., Miller, Kenneth B., Pihan, German A., Steensma, David P., Gibbons, Richard J., Higgs, Douglas R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2006
• Subjects: acquired thalassemia; Aged; alpha-Thalassemia - genetics; alpha‐thalassemia myelodysplastic syndrome; ATRX; chromatin remodeling factors; DNA Helicases - genetics; Exons; Humans; Male; Molecular Sequence Data; myelodysplastic syndrome; Myelodysplastic Syndromes - genetics; Nuclear Proteins - genetics; Point Mutation; X-linked Nuclear Protein
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.2006.00628.x

:  We describe a patient with acquired alpha‐thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66‐year‐old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3′ exon of the ATRX gene (CGA→TGA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q‐box element in ATRX function.