Rabbit Anti-Human ABCB7 (internal) Polyclonal antibody

Background. Sideroblastic anemias are heterogeneous congenital and acquired bone marrow disorders characterized by pathologic iron deposits in mitochondria of erythroid precursors. Among the congenital sideroblastic anemias (CSAs), the most common form is X-linked sideroblastic anemia, due to Mutations in 5-aminolevulinate synthase (ALAS2). A novel autosomal recessive CSA, caused by mutations in the erythroid specific mitochondrial transporter SLC25A38, was recently defined. Other known etiologies include mutations in genes encoding the thiamine transporter SLC19A2, the RNA-modifying enzyme pSeLldouridine synthase 1 (PUS1), a mitochondrial ATP-binding cassette transporter (ABCB7), glutaredoxin 5 (GLRX5), as well as mitochondrial DNA deletions. Despite these known diverse causes, in a Substantial portion of CSA cases a presumed genetic defect remains unknown. Procedure. In the context of the recent discovery of SLC25A38 as a major novel cause, we systematically analyzed a large cohort of previously unreported CSA patients. Sixty CSA probands (28 females, 32 males) were examined for ALAS2, SLC25A38, PUS1, GLRX5, and ABCB7 mutations. SLC19A2 and mitochondrial DNA were only analyzed if characteristic syndromic features were apparent. Results. Twelve probands had biallelic mutations in SLC25A38. Seven ALAS2 mutations were detected in eight sporadic CSA cases, two being novel. We also identified a novel homozygous null PUSI mutation and novel mitochondrial DNA deletions in two patients with Pearson syndrome. No mutations were encountered in GLRX5, ABCB7, or SLC19A2. Conclusions. The remaining undefined probands (43%) can be grouped according to gender, family, and clinical characteristics, suggesting novel X-linked and autosomal recessive forms of CSA. Pediatr Blood Cancer 2010;54:273-278. (C) 2009 Wiley-Liss, Inc.

Background: For most cases of idiopathic acquired sideroblastic anemia (IASA), the molecular pathogenesis is unknown, despite the consistent morphological signature of abundant pathological ringed sideroblasts with their characteristic iron-engorged mitochondria. Moderately elevated free erythrocyte protoporphyrin (FEP) levels have been described in IASA, suggesting that the activity of ferrochelatase, the enzyme that catalyzes the final step in heme biosynthesis (incorporation of ferrous iron into protoporphyrin), might be diminished in erythroid progenitor cells from IASA patients. Methods: We confirmed FEP elevation in IASA, then pursued a candidate gene approach that included screening the gene encoding ferrochelatase, FECH, for promoter and coding region mutations and mRNA expression changes in bone marrow from 37 patients with IASA. Results: The analytical techniques employed detected mutations in a test cohort of previously undiagnosed patients with biochemical evidence for erythropoietic protoporphyria, a condition resulting from germline mutations in FECH, but somatic missense mutations of FECH and its promoter were not observed in IASA patients. FECH was modestly overexpressed in progenitor cells from patients with IASA, compared with MDS patients without sideroblasts and healthy controls. In addition, we analyzed ABCB7 and PUS1, genes implicated in congenital sideroblastic anemia syndromes, but again found no coding mutations in acquired cases. Conclusion: We conclude that acquired mutations in the factors currently known to cause inherited sideroblastic anemias are uncommon in IASA. (c) 2006 Elsevier Ltd. All rights reserved.