Multiplex ligation‐dependent probe amplification screening of isolated increased HbF levels revealed three cases of novel rearrangements/deletions in the β‐globin gene cluster

• Published in: British journal of haematology Vol. 148; no. 1; pp. 154 - 160
• Main Authors: Lee, Seung‐Tae, Yoo, Eun‐Hyung, Kim, Ji‐Youn, Kim, Jong‐Won, Ki, Chang‐Seok
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2010; Blackwell
• Subjects: Aged; Base Sequence; beta-Globins - genetics; beta-Thalassemia - genetics; Biological and medical sciences; DNA Probes; Female; Fetal Hemoglobin - analysis; Fetal Hemoglobin - genetics; fusion gene; Gene Deletion; haemoglobin F; Hematologic and hematopoietic diseases; Hemoglobinopathies - genetics; hereditary persistence of fetal haemoglobin; Humans; Medical sciences; Middle Aged; Multigene Family; Polymerase Chain Reaction - methods; Gene cluster; haemoglobin F; Hematology; hereditary persistence of fetal haemoglobin; Beta-Peptide chain; Medical screening; Hereditary; Fetal hemoglobin; Persistence; Multiplex ligation dependent probe amplification; fusion gene; Gene rearrangement; Deletion; Fetus; Beta globin; Hybrid gene
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2009.07927.x

Summary Investigations of naturally occurring mutations, such as the deletional thalassaemias and hereditary persistence of fetal haemoglobins (HPFHs), have brought many insights into human globin switching, but limited data have been reported so far. We selected 15 individuals with elevated fetal haemoglobin (HbF) levels (>5%) from a previous screening of 27 006 Korean individuals and analysed dosage changes of the globin gene cluster using multiplex ligation‐dependent probe amplification (MLPA). Dosage changes detected by the MLPA probes were followed up with gap‐polymerase chain reaction and sequence analysis. Three subjects were found to have deletions in the globin gene cluster, including a β‐thalassaemia due to deletion of HBB (β‐globin gene), an HPFH due to deletions of HBD (δ‐globin gene) and HBB, and an HPFH due to a novel HBG2–HBG1 fusion gene consisting of exons 1 and 2 of HBG2 (Gγ‐globin gene) and exon 3 of HBG1 (Aγ‐globin gene). The case with the HBG2–HBG1 fusion suggested the existence of another mechanism for the reactivation of HBG2 and HBG1. The IVS2 of HBG2 and HBG1might play a role in HbF regulation, and combinations of specific polymorphisms could influence the reactivation of these genes in adults.