Paleari R, Paglietti E, Mosca A, Mortarino M, Maccioni L, Satta S, Cao A, Galanello R
Dipartimento di Scienze e Tecnologie Biomediche, Laboratorio Interdisciplinare Technologie Avanzare (L.I.T.A.), Università degli Studi, I-20090 Segrate, Milan, Italy.
Clin Chem. 1999 Jan;45(1):21-8.
Hemoglobin J Sardegna [alpha50(CD8)His-->Asn -->Asp] is a human Hb variant in which a posttranslational deamidation process takes place, transforming an Asn to an Asp residue. This variant, particularly widespread in northern Sardinia, has for the first time been characterized at the DNA level (codon 50 C-->A) on the selectively amplified alpha2-globin gene. We determined the protein and DNA sequences and performed cellulose acetate electrophoresis, isoelectric focusing, globin chain separation, stability tests with isopropanol and heat precipitation, and oxygen affinity analyses on whole blood to fully characterize the variant. A comprehensive review of the deamidation processes involving Asn and Gln residues in mutant proteins is reported, together with a discussion of the molecular mechanisms of such deamidations. Finally, examples of other proteins of clinical importance in which Asn or Gln residues have been implicated by DNA analysis alone are presented. These findings point out the importance of the complete characterization of variant proteins by use of both DNA and protein analyses.
