A family with multiple mutations and sequence variations in the α- and β-globin gene clusters

Background: Usually, laboratory diagnostics of hereditary hemoglobin disorders is fairly straightforward. Sometimes, however, correct diagnosis can be difficult. In this study, we describe a family with multiple mutations and sequence variations in the α- and (3-globin gene clusters. Methods: Hemocytometry results were obtained using an automated cell counter. Hemoglobin variant analysis was performed by cation-exchange HPLC. PCR and DNA sequence analyses were used to identify mutations in the globin genes. Results: The proposita was referred to our laboratory for hematological evaluation [hemoglobin 145 g/L (119-155 g/L) mean corpuscular volume 72 fl (80-97 fl), mean corpuscular hemoglobin 26 pg (28-36 pg), erythrocytes 5.6× 10 12 /L(3.7-5.0 10 12 /L)]. Characterization and quantification of hemoglobin variants showed 11.3% HbA 1 , 4.4% HbA 2 , 58.9% HbC and 23.0% HbF. Subsequent analysis revealed, in addition to a heterozygous HbC mutation, the presence of a β-thalassemia causing mutation (-90C>T), a heterozygous α-thalassemia (-α∼ 3.7 /αα) and three different γ-globin sequence variations. Additional molecular analysis was performed in all family members. Conclusions: In the family presented in this study, 10 different mutations were found in the globin genes. Molecular analysis was necessary to clarify hemoglobin variant analysis, in particular the low amount of HbA 1 in the proposita. Knowledge of the molecular background facilitates in the understanding of the hematological parameters and proper counseling of the patient.