Alloalbuminaemia and Analbuminaemia
Human serum albumin, the major blood protein, is encoded by a single autosomal gene, which lies at position 4q13.3, near the centromere of chromosome 4. Mutations in this gene may result in the presence of two circulating forms of the protein (bisalbuminaemia or alloalbuminaemia) or in the virtual absence of the protein from the blood (congenital analbuminaemia, CAA).
Alloalbumins are markers of migration and population genetics, and can provide an useful tool for the study of the unique binding properties of the protein. CAA is an extremely rare autosomal recessive disorder, characterised by a relatively mild phenotype, because of the compensatory increase of other serum proteins. In contrast to the benign presentation of CAA after birth, the pre- and peri-natal course appears less favourable, supporting the hypothesis that the rarity of the trait may be attributed to the fact that only a few analbuminaemic individuals survive past the neonatal state.
As part of a nearly thirty-years research project, we are continuing to study the molecular defects causing alloalbuminaemia and CAA in humans. Our research is aimed at improving the knowledge of the structure-function relationship for albumin and is addressed to shed light on the molecular basis underlying the analbuminaemic trait. The distribution of the mutations associated with CAA within the gene is shown in the top figure, whereas the localisation of the single amino acid substitutions found in alloalbumins in the three-dimensional structure of the protein is reported in the bottom figure (red spheres). Major information on this research can be found at the web-site www.albumin.org, which is presently managed by LM, MC, and by Dr. Ulrich Kragh-Hansen of the Aarhus University (Denmark).
Selected PapersCongenital analbuminaemia: Molecular defects and biochemical and clinical aspects. Minchiotti L, Galliano M, Caridi G, Kragh-Hansen U, Peters T Jr. Biochim Biophys Acta. 1830: 5494-502 (2013).
Human serum albumin isoforms: genetic and molecular aspects and functional consequences. Kragh-Hansen U, Minchiotti L, Galliano M, Peters T Jr. Biochim Biophys Acta 1830: 5405-17 (2013).
Mutations and Polymorphisms of the Gene of the Major Human Blood Protein, Serum Albumin. Minchiotti L, Galliano M, Kragh-Hansen U, Peters T Jr. Hum Mutat 29:1007-16 (2008).