title: Genetic regulation of fetal haemoglobin in inherited bone marrow failure syndromes.
abstract: Patients with inherited bone marrow failure syndromes (IBMFS) have 'stress erythropoiesis', with anaemia, macrocytosis, increased fetal haemoglobin (Hb F) and high erythropoietin levels. In haemoglobinopathies, Hb F levels are regulated by 3 quantitative trait loci, HBS1L-MYB, BCL11A and Xmn1-HBG2. In our study of 97 patients with an IBMFS, increased Hb F was associated with young age, male gender, anaemia, high erythropoietin levels, and alternative alleles in Xmn1-HBG2 [adjusted P = 0·04 for the total group, driven by Fanconi anaemia (P = 0·02) and dyskeratosis congenita (P = 0·09)]. Thus Hb F is regulated in IBMFS by Xmn1-HBG2, as it is in the haemoglobinopathies.
authors.affiliation: Clinical Genetics Branch, Division of Clinical Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DCEG/CGB Branch, 9609 Medical Center Dr, Rm 6E452, Bethesda, MD 20892, USA. alterb@mail.nih.gov
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Day
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.forename: Neelam
authors.initials: N
authors.lastname: Giri
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000741:Anemia, Aplastic; D029503:Anemia, Diamond-Blackfan / Q000097:blood / Q000235:genetics; D001855:Bone Marrow Diseases / Q000097:blood / Q000235:genetics; D000080983:Bone Marrow Failure Disorders; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019871:Dyskeratosis Congenita / Q000097:blood / Q000235:genetics; D010188:Exocrine Pancreatic Insufficiency / Q000097:blood / Q000235:genetics; D005199:Fanconi Anemia / Q000097:blood / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020570:Genes, myb; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000235:genetics*; D006801:Humans; D008068:Lipomatosis / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012097:Repressor Proteins; D000081003:Shwachman-Diamond Syndrome; D055815:Young Adult; D055545:gamma-Globins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055545:gamma-Globins; D005319:Fetal Hemoglobin
keywords: Fanconi anaemia; dyskeratosis congenita; fetal haemoglobin; inherited bone marrow failure syndromes; quantitative trait loci