title: Hb Cardarelli [beta86(F2)Ala-->Pro]: a new unstable and hyperaffine variant in association with beta(+)-thalassemia.
abstract: Hb Cardarelli [beta86(F2)Ala-->Pro] is a new unstable and high oxygen affinity variant found in several members of a family from Naples, Southern Italy. A detailed structural and functional characterization of the variant was performed on two subjects, at both the protein and DNA level. The first patient exhibited 43% of the variant hemoglobin (Hb) without major hematological problems. The proband showed 82% of the abnormal Hb in association with beta(+)-thalassemia (thal) that caused relevant erythrocytosis requiring frequent phlebotomies. Structural investigation of the Hb variant by mass spectrometric methodologies identified the amino acid replacement as Ala-->Pro at beta86. The corresponding DNA mutation GCC-->CCC at codon 86 of the beta-globin gene was assessed by both DNA sequencing and amplification refractory mutation system (ARMS) techniques. Functional studies carried out on whole blood and diluted hemolysates from both patients demonstrated increased oxygen affinity, decreased Bohr effect, reduced heme-heme interaction and nearly halved 2,3-diphosphoglycerate (2,3-DPG) and chloride effects.
authors.affiliation: Centro Microcitemie A. Mastrobuoni, Azienda Ospedale Cardarelli, Napoli, Italia.
authors.forename: Leonilde
authors.initials: L
authors.lastname: Pagano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salzano
authors.forename: Virginia
authors.initials: V
authors.lastname: Carbone
authors.forename: Daniela
authors.initials: D
authors.lastname: Iannelli
authors.forename: Assunta
authors.initials: A
authors.lastname: Viola
authors.forename: Filiberto
authors.initials: F
authors.lastname: Pollio
authors.forename: Luciano
authors.initials: L
authors.lastname: Prossomariti
authors.forename: Onorata
authors.initials: O
authors.lastname: David
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ricco
authors.forename: Piero
authors.initials: P
authors.lastname: Pucci
mesh_terms: D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000737:chemistry; D010375:Pedigree; D011086:Polycythemia / Q000209:etiology; D011392:Proline / Q000235:genetics; D013379:Substrate Specificity / Q000235:genetics; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; C496305:hemoglobin Cardarelli; D005914:Globins; D011392:Proline; D000409:Alanine; D010100:Oxygen