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: Blanche P Alter, Philip S Rosenberg, Thomas Day, Stephan Menzel, Neelam Giri, Sharon A Savage, Swee Lay Thein
• Journal: British journal of haematology (Br J Haematol) Vol. 162 Issue 4 Pg. 542-6 (Aug 2013) ISSN: 1365-2141 [Electronic] England
• PMID: 23713742 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Chemical References

• BCL11A protein, human
• Carrier Proteins
• Nuclear Proteins
• Repressor Proteins
• gamma-Globins
• Fetal Hemoglobin

Topics

• Adolescent
• Adult
• Alleles
• Anemia, Aplastic
• Anemia, Diamond-Blackfan (blood, genetics)
• Bone Marrow Diseases (blood, genetics)
• Bone Marrow Failure Disorders
• Carrier Proteins (genetics)
• Child
• Child, Preschool
• Dyskeratosis Congenita (blood, genetics)
• Exocrine Pancreatic Insufficiency (blood, genetics)
• Fanconi Anemia (blood, genetics)
• Female
• Fetal Hemoglobin (biosynthesis, genetics)
• Gene Expression Regulation, Developmental
• Genes, myb
• Hemoglobinuria, Paroxysmal (blood, genetics)
• Humans
• Lipomatosis (blood, genetics)
• Male
• Middle Aged
• Nuclear Proteins (genetics)
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci
• Repressor Proteins
• Shwachman-Diamond Syndrome
• Young Adult
• gamma-Globins (biosynthesis, genetics)