title: A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gàmbara [beta 82(EF6)Lys-->Glu].
abstract: Hb Gàmbara is a new hemoglobin variant with abnormal beta chains that has been found in three out of four members of a family of Lombardy origin (Gàmbara, Brescia, Northern Italy). The affected subjects led a normal life, but they had modest erythrocytosis and mild (compensated) hemolysis with slight splenomegaly. Their abnormal hemoglobin was about 52% of the total hemoglobin, and was shown to be stable by the isopropanol test. Whole blood P50 of the proband was 19.3 Torr, Bohr effect was decreased (-0.25), as well as the molar ratio between the 2,3-diphosphoglycerate level and total hemoglobin of erythrocytes (0.68). The purified abnormal hemoglobin was characterized by an altered oxygen affinity, low n-factor, chloride, and 2,3-diphosphoglycerate effects. The Bohr effect was about 40% of the normal control. The abnormal hemoglobin moved faster than Hb A at alkaline electrophoresis, and split into two fractions, probably due to the formation of hybrid tetramers (alpha 2 beta A beta X). The reversed phase high performance liquid chromatogram from the tryptic digest of the aminoethylated abnormal beta chain subunits indicated the presence of an extra peptide, beta T-9, 10, replacing the individual peptides beta T-9 and beta T-10. Finally, the proband's DNA, drawn from a suitable segment of the beta structural gene (exon 2), revealed a nucleotide sequence carrying the heterozygous mutation AAG-->GAG at codon 82. This led to a Lys-->Glu substitution at position 82(EF6) of the beta chain.
authors.affiliation: Centro della Microcitemie, Ospedali Galliera, Genova, Italia.
authors.forename: G
authors.initials: G
authors.lastname: Ivaldi
authors.forename: V
authors.initials: V
authors.lastname: Scimè-Degani
authors.forename: O
authors.initials: O
authors.lastname: David
authors.forename: M
authors.initials: M
authors.lastname: Baffico
authors.forename: M
authors.initials: M
authors.lastname: Baldi
authors.forename: D
authors.initials: D
authors.lastname: Leone
authors.forename: M
authors.initials: M
authors.lastname: Mazzocco
authors.forename: L
authors.initials: L
authors.lastname: Leone
authors.forename: A
authors.initials: A
authors.lastname: Piga
authors.forename: E
authors.initials: E
authors.lastname: Furian
authors.forename: G
authors.initials: G
authors.lastname: Ricco
mesh_terms: D004586:Electrophoresis; D004912:Erythrocytes / Q000473:pathology; D005973:Glutamine; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008239:Lysine; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011086:Polycythemia / Q000235:genetics* / Q000473:pathology
chemical_list: D006455:Hemoglobins, Abnormal; C108108:hemoglobin Gambara; D005973:Glutamine; D008239:Lysine