ALLOALBUMINEMIA IN SWEDEN - STRUCTURAL STUDY AND PHENOTYPIC DISTRIBUTION OF 9 ALBUMIN VARIANTS

Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutations were identified by protein-structural analysis followed by allele-specific DNA hybridization to verify the most common types. Slightly retarded (+1) mobility was seen in 80 cases. Of these, 71 had the Arg-2 --> Cys proalbumin variant previously called Malmo I proalbumin. Thirteen examples of the second most frequent type, the substitution Lys313 --> Asn and a mobility change of -1 charge unit, were found, as well as six cases of Glu570 --> Lys (albumin B) and a single case of Arg-1 --> Gln (proalbumin Christchurch). Five previously unreported types of alloalbuminemia were identified: four instances of Glu376 --> Gln, which is the second known mutation at this site; two examples of Asp550 --> Ala, the second mutation reported at this site; and one example each of Asp63 --> Asn, Gln268 --> Arg, and Asn318 --> Lys. Other mutations were identified among eight subjects of foreign descent. The high frequency and relatively uniform geographic distribution of the Arg-2 --> Cys mutation suggest that it may have occurred in a founder individual many generations ago in Sweden.