Hb Den Haag [β45(CD4)Phe→Tyr]. A New Hemoglobin Variant Observed During Early Pregnancy Diagnostics

Abstract

During a second pilot study, intended to explore the possibility of a country wide implementation of carrier diagnostics for hemoglobinopathies in The Netherlands, we observed a new abnormal hemoglobin (Hb) variant in three members of a family of Scandinavian origin living in the Dutch city of The Hague (Den Haag). The proband, a 34-year-old female presented with low Hb, packed cell volume (PCV) and red blood cell (RBC) values but was normocytic and normochromic. High performance liquid chromatography (HPLC) analysis revealed a partially separated fraction following Hb A. Molecular diagnostics disclosed a TTT>TAT transversion at HBB:c.137 causing a Phe→Tyr single amino acid substitution at position 45 of the β-globin gene. Previously described heterozygous mutations at the same position [Hb Cheverly (Phe→Ser) and Hb Arta (Phe→Cys)] were reported to be associated with mild chronic hemolysis similar to this case. We describe the hematological features of the six family members, the biochemical and molecular data and we discuss the possible consequences in combination with the common β-thalassemia (β-thal) trait.

Keywords:

• Hemoglobinopathies
• Hemolysis
• Early pregnancy
• Prevention

ACKNOWLEDGMENTS

Part of this study was supported by the European Commission grant for the “e-Infrastructure for Thalassaemia Research Network,” Coordination Action, Contract no. 026539, and by the Dutch Zon-Mw project nr. 21000.0105. We are grateful to Dr. Henri Wajcman (INSERM U841, Créteil, France) for assistance in calculating the invariability of phenylalanine.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.