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. 1994 Sep 27;91(20):9417–9421. doi: 10.1073/pnas.91.20.9417

Analbuminemia: three cases resulting from different point mutations in the albumin gene.

S Watkins 1, J Madison 1, M Galliano 1, L Minchiotti 1, F W Putnam 1
PMCID: PMC44823  PMID: 7937781

Abstract

Analbuminemia is a very rare recessive disorder in which subjects have little or no circulating albumin, although albumin is normally the most abundant plasma protein and has many functions. Analbuminemia is caused by a variety of mutations in the albumin gene and is exhibited only by subjects homozygous for the defect. Previously the mutation had been identified at the molecular level in only two human cases; in one case it resulted from an exon-splicing defect, and in the other case it was caused by a nucleotide insertion that caused a frameshift and premature stop codon. In this investigation we identified the mutations in three unrelated subjects from different countries. In each instance a single-nucleotide mutation produced a stop codon, but the mutations occurred at three different sites: (i) in an Italian male a C-->T transition at nt 2368 in the genomic sequence of albumin, (ii) a C-->T transition at nt 4446 for an American female, and (iii) a G-->A transition at nt 7708 in a Canadian male. The size of the albumin fragment that might have been produced for the three cases varied from 31- to 213-amino acid residues, but no evidence for a circulating albumin fragment was obtained. The paradox is that analbuminemia is extremely rare (frequency < 1 x 10(6)); yet the virtual absence of albumin is tolerable despite its multiple functions.

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Selected References

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  1. BENNHOLD H., KALLEE E. Comparative studies on the half-life of I 131-labeled albumins and nonradioactive human serum albumin in a case of analbuminemia. J Clin Invest. 1959 May;38(5):863–872. doi: 10.1172/JCI103868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldo-Enzi G., Baiocchi M. R., Vigna G., Andrian C., Mosconi C., Fellin R. Analbuminaemia: a natural model of metabolic compensatory systems. J Inherit Metab Dis. 1987;10(4):317–329. doi: 10.1007/BF01799973. [DOI] [PubMed] [Google Scholar]
  3. Baldo G., Fellin R., Manzato E., Baiocchi M. R., Ongaro G., Baggio G., Fabiani F., Pauluzzi S., Crepaldi G. Characterization of hyperlipidemia in two patients with analbuminemia. Clin Chim Acta. 1983 Mar 14;128(2-3):307–319. doi: 10.1016/0009-8981(83)90330-3. [DOI] [PubMed] [Google Scholar]
  4. Boman H., Hermodson M., Hammond C. A., Motulsky A. G. Analbuminemia in an American Indian girl. Clin Genet. 1976 May;9(5):513–526. doi: 10.1111/j.1399-0004.1976.tb01606.x. [DOI] [PubMed] [Google Scholar]
  5. Brennan S. O., Arai K., Madison J., Laurell C. B., Galliano M., Watkins S., Peach R., Myles T., George P., Putnam F. W. Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene. Proc Natl Acad Sci U S A. 1990 May;87(10):3909–3913. doi: 10.1073/pnas.87.10.3909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bélanger L., Roy S., Allard D. New albumin gene 3' adjacent to the alpha 1-fetoprotein locus. J Biol Chem. 1994 Feb 25;269(8):5481–5484. [PubMed] [Google Scholar]
  7. Carlson J., Sakamoto Y., Laurell C. B., Madison J., Watkins S., Putnam F. W. Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8225–8229. doi: 10.1073/pnas.89.17.8225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carter D. C., Ho J. X. Structure of serum albumin. Adv Protein Chem. 1994;45:153–203. doi: 10.1016/s0065-3233(08)60640-3. [DOI] [PubMed] [Google Scholar]
  9. Cormode E. J., Lyster D. M., Israels S. Analbuminemia in a neonate. J Pediatr. 1975 Jun;86(6):862–867. doi: 10.1016/s0022-3476(75)80215-0. [DOI] [PubMed] [Google Scholar]
  10. Erstad B. L., Gales B. J., Rappaport W. D. The use of albumin in clinical practice. Arch Intern Med. 1991 May;151(5):901–911. [PubMed] [Google Scholar]
  11. Esumi H., Takahashi Y., Sato S., Nagase S., Sugimura T. A seven-base-pair deletion in an intron of the albumin gene of analbuminemic rats. Proc Natl Acad Sci U S A. 1983 Jan;80(1):95–99. doi: 10.1073/pnas.80.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Frohlich J., Pudek M. R., Cormode E. J., Sellers E. M., Abel J. G. Further studies on plasma proteins, lipids, and dye- and drug-binding in a child with analbuminemia. Clin Chem. 1981 Jul;27(7):1213–1216. [PubMed] [Google Scholar]
  13. Galliano M., Minchiotti L., Porta F., Rossi A., Ferri G., Madison J., Watkins S., Putnam F. W. Mutations in genetic variants of human serum albumin found in Italy. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8721–8725. doi: 10.1073/pnas.87.22.8721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Madison J., Arai K., Sakamoto Y., Feld R. D., Kyle R. A., Watkins S., Davis E., Matsuda Y., Amaki I., Putnam F. W. Genetic variants of serum albumin in Americans and Japanese. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9853–9857. doi: 10.1073/pnas.88.21.9853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Madison J., Galliano M., Watkins S., Minchiotti L., Porta F., Rossi A., Putnam F. W. Genetic variants of human serum albumin in Italy: point mutants and a carboxyl-terminal variant. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6476–6480. doi: 10.1073/pnas.91.14.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Minghetti P. P., Ruffner D. E., Kuang W. J., Dennison O. E., Hawkins J. W., Beattie W. G., Dugaiczyk A. Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747–6757. [PubMed] [Google Scholar]
  17. Mullis K., Faloona F., Scharf S., Saiki R., Horn G., Erlich H. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):263–273. doi: 10.1101/sqb.1986.051.01.032. [DOI] [PubMed] [Google Scholar]
  18. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  19. Peters T., Jr Serum albumin. Adv Protein Chem. 1985;37:161–245. doi: 10.1016/s0065-3233(08)60065-0. [DOI] [PubMed] [Google Scholar]
  20. Shalaby F., Shafritz D. A. Exon skipping during splicing of albumin mRNA precursors in Nagase analbuminemic rats. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2652–2656. doi: 10.1073/pnas.87.7.2652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Takahashi N., Takahashi Y., Isobe T., Putnam F. W., Fujita M., Satoh C., Neel J. V. Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8001–8005. doi: 10.1073/pnas.84.22.8001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tanaka H., Matsuhisa A., Nagamori S., Shimizu K., Niiya M., Ohno T., Nagase S. Characteristics and significance of albumin-positive hepatocytes in analbuminemic rats. Eur J Cell Biol. 1990 Dec;53(2):267–274. [PubMed] [Google Scholar]
  23. WALDMANN T. A., GORDON R. S., Jr, ROSSE W. STUDIES ON THE METABOLISM OF THE SERUM PROTEINS AND LIPIDS IN A PATIENT WITH ANALBUMINEMIA. Am J Med. 1964 Dec;37:960–968. doi: 10.1016/0002-9343(64)90136-6. [DOI] [PubMed] [Google Scholar]
  24. Watkins S., Madison J., Davis E., Sakamoto Y., Galliano M., Minchiotti L., Putnam F. W. A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5959–5963. doi: 10.1073/pnas.88.14.5959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Watkins S., Madison J., Galliano M., Minchiotti L., Putnam F. W. A nucleotide insertion and frameshift cause analbuminemia in an Italian family. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2275–2279. doi: 10.1073/pnas.91.6.2275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Watkins S., Sakamoto Y., Madison J., Davis E., Smith D. G., Dwulet J., Putnam F. W. cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2409–2413. doi: 10.1073/pnas.90.6.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. White M. B., Carvalho M., Derse D., O'Brien S. J., Dean M. Detecting single base substitutions as heteroduplex polymorphisms. Genomics. 1992 Feb;12(2):301–306. doi: 10.1016/0888-7543(92)90377-5. [DOI] [PubMed] [Google Scholar]

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