X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations.

Research paper by Dean R DR Campagna, Charlotte I CI de Bie, Klaus K Schmitz-Abe, Marion M Sweeney, Anoop K AK Sendamarai, Paul J PJ Schmidt, Matthew M MM Heeney, Helger G HG Yntema, Caroline C Kannengiesser, Bernard B Grandchamp, Charlotte M CM Niemeyer, Nine V A M NV Knoers, Sonia S Swart, Gordon G Marron, Richard R van Wijk, et al.

Indexed on: 30 Oct '13Published on: 30 Oct '13Published in: American Journal of Hematology


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.