title: The role of X-inactivation in the gender bias of patients with acquired alpha-thalassaemia and myelodysplastic syndrome (ATMDS).
abstract: Alpha thalassaemia myelodysplastic syndrome (ATMDS) is an unusual complication of chronic myeloid malignancy that is associated with a striking red cell phenotype. It represents an acquired form of alpha-thalassaemia that most commonly arises in the context of myelodysplasia. It has recently been shown that this condition occurs in association with somatic mutations of a known X-encoded trans-acting regulator of alpha globin gene (HBA) expression, ATRX. There is an unexplained, strong male preponderance of individuals with the ATMDS phenotype with a >5:1 male-female ratio and furthermore, all the somatic ATRX mutations described to date have been in males. Here we report the identification, in a single centre, of two females with ATMDS and mutations in the ATRX gene, proving that ATMDS associated with such mutations may occur, albeit rarely, in females. It seemed possible that females might be less likely to develop ATMDS if the inactivated copy of the ATRX gene (ATRX) became progressively re-activated throughout life. This study ruled out this hypothesis by investigating the pattern of ATRX inactivation in a cross-sectional analysis of normal females at ages ranging from newborn to 90 years.
authors.affiliation: Division of Haematology and Oncology, University of Freiburg Medical Centre, Freiburg, Germany.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Haas
authors.forename: Noemi B A
authors.initials: NB
authors.lastname: Roy
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Deville
authors.forename: Chris
authors.initials: C
authors.lastname: Fisher
authors.forename: Michael
authors.initials: M
authors.lastname: Schwabe
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bissé
authors.forename: Alain
authors.initials: A
authors.lastname: van Dorsselaer
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Higgs
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D004265:DNA Helicases / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D017678:Sex Distribution; D049951:X Chromosome Inactivation; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000235:genetics* / Q000473:pathology
chemical_list: D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein