Korean J Lab Med.  2010 Jun;30(3):307-311. 10.3343/kjlm.2010.30.3.307.

Clinical Characteristics and ALB Gene Mutation Analysis of Korean Patients with Bisalbuminemia

• Kim YH
• Lee YW
• Jeon BR
• Lee YK
• Shin HB
• Kang DH
• Park SK
• Hong DS
• Lee ST
• Kim JW
• Ki CS

• KMID: 1781632
• DOI: http://doi.org/10.3343/kjlm.2010.30.3.307

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.

Keyword

Bisalbuminemia; Albumin; ALB; Mutation; Korean

MeSH Terms

Aged
Amino Acid Substitution
Asian Continental Ancestry Group/*genetics
Blood Protein Disorders/diagnosis/*genetics
Female
Humans
Male
Middle Aged
Mutation, Missense
Point Mutation
Protein Binding
Protein Structure, Tertiary
Republic of Korea
Serum Albumin/*genetics

Figure

• 

  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.

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