title: X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations.
abstract: X-linked sideroblastic anemia (XLSA) is the most common form of congenital sideroblastic anemia. In affected males, it is uniformly associated with partial loss-of-function missense mutations in the erythroid-specific heme biosynthesis protein 5-aminolevulinate synthase 2 (ALAS2). Here, we report five families with XLSA owing to mutations in a GATA transcription factor binding site located in a transcriptional enhancer element in intron 1 of the ALAS2 gene. As such, this study defines a new class of mutations that should be evaluated in patients undergoing genetic testing for a suspected diagnosis of XLSA.
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Dean R
authors.initials: DR
authors.lastname: Campagna
authors.forename: Charlotte I
authors.initials: CI
authors.lastname: de Bie
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmitz-Abe
authors.forename: Marion
authors.initials: M
authors.lastname: Sweeney
authors.forename: Anoop K
authors.initials: AK
authors.lastname: Sendamarai
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Schmidt
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Heeney
authors.forename: Helger G
authors.initials: HG
authors.lastname: Yntema
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
authors.forename: Sonia
authors.initials: S
authors.lastname: Swart
authors.forename: Gordon
authors.initials: G
authors.lastname: Marron
authors.forename: Richard
authors.initials: R
authors.lastname: van Wijk
authors.forename: Reinier A
authors.initials: RA
authors.lastname: Raymakers
authors.forename: Alison
authors.initials: A
authors.lastname: May
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Markianos
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: Bottomley
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D000328:Adult; D000368:Aged; D000756:Anemia, Sideroblastic / Q000097:blood / Q000235:genetics*; D001665:Binding Sites; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005260:Female; D050980:GATA Transcription Factors / Q000378:metabolism*; D040181:Genetic Diseases, X-Linked / Q000097:blood / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
chemical_list: D050980:GATA Transcription Factors; D000624:5-Aminolevulinate Synthetase; C480079:ALAS2 protein, human