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A long-term electrophoretic survey on plasma proteins, which was carried out in several clinical laboratories in Italy, identified 28 different genetic variants of human serum albumin and four cases of analbuminemia. We have previously characterized 16 point mutations, 3 C-terminal mutants, and the genetic defects in two analbuminemic subjects. Here, we report the molecular defects of four alloalbumins that have been characterized by protein structural analysis. Of these, three represent new single-point mutations: albumins Tregasio, Val122→Glu, Bergamo, Asp314→Gly, and Maddaloni, Va1533→Met. The fourth, albumin Besana Brianza, has the same Asp494→Asn mutation that introduces a glycosylation site which has been previously reported in a variant from New Zealand, albumin Casebrook. However, in contrast to albumin Casebrook, albumin Besana Brianza is only partially glycosylated and the oligosaccharide is heterogeneous, consisting of a biantennary complex type N-glycan with either two or one sialic acid residue(s) on the antennae. Both albumin Maddaloni and Besana Brianza represent mutations at hypermutable CpG dinucleotide sites; albumin Maddaloni is a mutant that does not involve a charged amino acid. [ABSTRACT FROM AUTHOR]

The authors have investigated the possibility that the Ferrara type of β-thalassemia, in which β-globulin synthesis is absent, may be due to a nonsense mutation on the gene for β-globin. This hypothesis has been tested by trying to detect the presence of newly synthesized β-globin fragments in the reticulocytes of homozygous β-thalassemic subjects. The red blood cells were incubated with [3H]leucine. The whole hemolysate was hydrolyzed with trypsin and several β-chain peptides were isolated by column chromatography and assayed for radioactivity. No incorporation of radioactive leucine could be detected in the various β-globin peptides isolated and examined. The hypothesis that a nonsense mutation is responsible for the absence of β-globin synthesis in the Ferrara β-thalassemia is not supported by these findings. [ABSTRACT FROM AUTHOR]