A novel 17.9 kb deletion of the beta-globin gene causing beta-thalassemia trait in a Danish male

BACKGROUND: Beta-thalassemia is a common monogenic disease, especially in malaria-endemic areas. It is mainly caused by point mutations in the beta-globin gene (HBB) while large deletions are more rarely described. Here, a novel, large deletion encompassing the entire HBB gene causing beta-thalassemia in an ethnically Danish male is described.

CASE REPORT: A 60-year-old male with no family history of anemia was admitted to the local Department of Medicine with microcytotic anemia. He had observed fatigue and slight dizziness, but despite this, he felt healthy. His blood tests showed no signs of iron deficiency and a hemoglobinopathy was suspected. Hemoglobin fractionation by ion-exchange high-performance liquid chromatography revealed an elevated HbF of 5.9 % and an increased HbA2 of 8.5 %. GAP-PCR of the alpha-thalassemia HBA1/HBA2 genes and Sanger sequencing of the HBB gene showed none of the common thalassemia-causing variations. Hence, multiplex ligation dependent probe amplification was performed and a deletion variant was identified that resulted in the complete loss of the HBB gene. The exact breakpoints were identified using Sanger sequencing, revealing a novel 17.9 kb deletion (NC000011.10:g.5211831_5229725del) not previously described in the literature or in databases. The deletion was consistent with beta-thalassemia trait in accordance with the patient's symptoms.

CONCLUSION: We present a novel large deletion of the HBB gene causing beta-thalassemia trait detected in an ethnically Danish male. Thalassemia must be considered in patients with microcytosis of unknown cause despite a Northern European ethnicity.