A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gàmbara [beta 82(EF6)Lys-->Glu].
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.
Ivaldi
G
G
Centro della Microcitemie, Ospedali Galliera, Genova, Italia.
Scimè-Degani
V
V
David
O
O
Baffico
M
M
Baldi
M
M
Leone
D
D
Mazzocco
M
M
Leone
L
L
Piga
A
A
Furian
E
E
Ricco
G
G
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
D006455:Hemoglobins, Abnormal; C108108:hemoglobin Gambara; D005973:Glutamine; D008239:Lysine