Hb Haaglanden: a new nonsickling β7Glu>Val variant. Consequences for basic diagnostics, screening, and risk assessment when dealing with HbS-like variants

• Published in: International journal of laboratory hematology 2012-10, Vol.34 (5), p.551-555
• Main Authors: HARTEVELD, C. L., PONJEE, G., BAKKER-VERWEIJ, M., ARKESTEIJN, S. G. J., PHYLIPSEN, M., GIORDANO, P. C.
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Substitution; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - diagnosis; Anemia, Sickle Cell - genetics; Base Sequence; beta-Globins - genetics; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Electrophoresis, Capillary; Genetic Testing; HbS; Hemoglobin, Sickle - genetics; Hemoglobins, Abnormal - genetics; Humans; Male; Point Mutation; Risk Assessment; Risk Factors; sickle cell disease; sickle test
• ISSN: 1751-5521; 1751-553X
• DOI: 10.1111/j.1751-553X.2012.01424.x

Summary Introduction:  To report a new hemoglobin variant undistinguishable from the common HbS on HPLC. To show the efficiency of the simplest confirmation method for HbS and to discuss the implications that may occur if HbS‐like variants are wrongly reported as HbS. Methods:  Basic hematology, separation and measurement of the Hb fractions, ‘sickle test,’ and molecular analysis. Results:  The abnormal Hb fractions were eluting in the HbS window on HPLC, sickle test was however negative, and DNA sequencing of the beta globin gene revealed an unclassified variant HBBc.23A>T, p.Glu8Val in heterozygous form. Conclusions:  Although the amino acid substitution of this new variant is identical to that of HbS and shifted of a single amino acid position, no polymerization occurs in vitro. The sickle test is a valid method to confirm or exclude HbS trait in individual cases. Whenever the case is part of a possible couple at risk, then one has to use full DNA analysis in both partners not to miss hidden concomitant defects important for genetic risk predictions.