Novel Hemoglobin (Hb Grey Lynn) Substitution (α91Leu→Phe) Affects Heme Interactions and α1β2 Contacts

[摘要] Since the discovery of the causative mutation of sickle cell anemia, hemoglobinopathies have become the iconic molecular diseases, with some 900 mutations reported to date (http://globin.cse.psu.edu). Detection and characterization of novel mutations, facilitated by increasingly sensitive analytical techniques, continue to shed light on how molecular structure and function are preserved in the tetrameric molecule. Here we report the identification of a novel α chain substitution (α91Leu→Phe) in a patient who was also heterozygous for the αSEA 2-gene deletion.A full blood count on this 40-year-old woman revealed a microcytic picture with a hemoglobin (Hb) concentration of 103 g/L, a mean cell volume of 63 fL, and a hematocrit of 0.33. These results prompted a hemoglobinopathy/thalassemia screen that revealed a normal cellulose acetate electrophoresis pattern, a marginally positive isopropanol stability test, and values within reference intervals for HbA2 (3.0%), HbF (2%), and reticulocytes. Occasional HbH bodies were seen, and the Bio-Rad Variant cation exchange system for β-thalasaemia revealed an aberrant component of 35.5% in the HbA2 window.Examination of whole lysate by electrospray ionization mass spectrometry on a VG Platform (1 …

[学科分类] 过敏症与临床免疫学