title: Hb Den Haag [beta45(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 beta-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 beta-thalassemia (beta-thal) trait.
authors.affiliation: The Reference Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Judith O
authors.initials: JO
authors.lastname: Kaufmann
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Margreet
authors.initials: M
authors.lastname: Bakker-Verweij
authors.forename: Sandra G J
authors.initials: SG
authors.lastname: Arkesteijn
authors.forename: Peter
authors.initials: P
authors.lastname: van Delft
authors.forename: Hans
authors.initials: H
authors.lastname: Haak
authors.forename: Pierre W
authors.initials: PW
authors.lastname: Wijermans
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kerkhoffs
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006453:Hemoglobinopathies / Q000175:diagnosis*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D009426:Netherlands; D010375:Pedigree; D010865:Pilot Projects; D017354:Point Mutation / Q000235:genetics*; D011296:Prenatal Diagnosis; D013997:Time Factors
chemical_list: D006455:Hemoglobins, Abnormal