Genetic variants showing apparent hot-spots in the human serum albumin gene

The molecular defects of three different slow-migrating genetic variants of human serum albumin, albumins Kamloops (formerly RM), Stirling and Amsterdam, previously characterized only by electrophoretic and dye-binding studies, are now reported. Two of them are proalbumin variants: sequential analysis of the purified whole proteins has established the mutation responsible for albumin Kamloops as -1Arg --> Gln, and for albumin Stirling as - 2Arg --> His. A Glu --> Lys substitution in position 570 of the mature albumin molecule was determined in albumin Amsterdam by sequential analysis of two abnormal tryptic fragments. The three alloalbumins are caused by single-base changes all of which seem to represent hot-spots in the albumin gene. The possible functional consequences of the presence of a circulating alloalbumin are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.