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Abstract
Background:
Bisalbuminemia is a hereditary or an acquired condition characterized by the presence of 2 albumin variants with different mobilities on serum protein electrophoresis (SPE). The clinical significance of bisalbuminemia has not been clearly established. However, some regions of the albumin variant may affect the biochemical analysis of biomolecules such as steroid or thyroid hormones by altering their albumin-binding affinities. In this study, we analyzed the clinical manifestations, genetic variations, and the albumin-binding characteristics in Korean patients with bisalbuminemia.
Methods:
We performed SPE for samples from 580 Korean subjects and identified bisalbuminemia on the basis of the results of SPE. The clinical and biochemical characteristics, ALB gene mutations, and the structures of the albumin variants of patients with bisalbuminemia were analyzed.
Results:
SPE showed bisalbuminemia in 2 patients. One patient showed a genetic variation known as Nagasaki-1 (Asp293Gly) and the other showed a hitherto unreported missense mutation (c.593A>T; Lys198Ile). In both cases, the serum concentrations of the substances with binding affinity for albumin were not affected, and the mutation sites of the albumin were not located with the protein-binding loci.
Conclusions:
The 2 Korean patients with bisalbuminemia showed genetic variations, including a novel missense mutation. The ALB gene analysis with 3D modeling is useful for determining the nature of bisalbuminemia and for predicting the effects on the albumin-binding affinity of other biochemical compounds.
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Fig. 1.
Capillary electrophoreses of the serum proteins of patient 1 (A) and patient 2 (B) with bisalbuminemia. Two peaks were observed at the albumin region. Solid arrows indicate the characteristic peak of albumin. A 1:1 mixture of the serum of normal control and that of patient 2 showed an abnormal albumin peak (open arrow) with a low peak height (C).
Fig. 2.
Mutation analysis of the albumin (ALB) gene. Direct sequencing of the ALB gene shows overlapping peaks (arrow) at nucleotide position 878 in patient 1 due to a heterozygous A to G transition (c.878A>G; D298G) (A) and at the nucleotide position 593 in the patient 2 due to a heterozygous A to T transversion (c.593A>T; K198I) (B).
Fig. 3.
Ribbon diagram of a monomer of human albumin of Korean patients with bisalbuminemia; the locations of the amino acid replacements are depicted. The substituted amino acid residues are indicated in red.
Table 1.
Biochemical analysis of the components that show a binding affinity to albumin
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