title: Hb San Cataldo [β144(HC1)Lys→Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen.
abstract: A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband.
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Vinciguerra
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Passarello
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Cassarà
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Leto
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cannata
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Crivello
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.
authors.forename: Veronica
authors.initials: V
authors.lastname: Di Salvo
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
authors.affiliation: a Department of Hematology and Rare Diseases , Unit of Rare Diseases of Blood and Blood-Forming Organs, Villa Sofia-Cervello Hospital , Palermo , Italy and.|b Department of Hematology and Rare Diseases , Unit for Molecular Diagnosis of Rare Diseases, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital , Palermo , Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Giambona
mesh_terms: D019794:2,3-Diphosphoglycerate; D003937:Diagnosis, Differential; D005260:Female; D006453:Hemoglobinopathies / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010100:Oxygen / Q000378:metabolism*; D011087:Polycythemia Vera / Q000209:etiology / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; D010100:Oxygen
keywords: Genetic counseling; hemoglobin (Hb) variant; hemoglobinopathies; increased oxygen affinity; screening program