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Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele

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Summary

The enzyme, lecithin cholesterol acyltransferase (LCAT), is responsible for the esterification of plasma cholesterol mediating the transfer of an acyl group from lecithin to the 3-hydroxy group of cholesterol. Deficiency of the enzyme is a well-known syndrome with a widespread geographic occurrence. We have cloned an allele from a patient homozygous for the LCAT deficiency. The only change that we could detect is a C to T transition in the fourth exon of the gene; this causes a substitution of Arg for Trp at position 147 of the mature protein. The functional significance of such a substitution with respect to the enzyme defect was demonstrated by transfecting the mutated LCAT gene in the cell line COS-1.

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References

  • Adrian G, Hutton J (1983) Adenosine deamidase messanger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency. J Clin Invest 71:1649–1660

    Google Scholar 

  • Albers J, Utermann G (1981) Genetic control of lecithin-cholesterol acyltransferase: measurement of LCAT man in a large kindred with LCAT deficiency. Am J Hum Genet 33:702–708

    Google Scholar 

  • Avogaro P, Bittolo Bon G, Cazzolato G, Quinci G, Belussi F (1978) Levels and chemical composition of HDL2, HDL3 and other major lipoprotein classes in survivers of myocardic infarction. Artery 5:495–508

    Google Scholar 

  • Benton W, Davis R (1977) Screening lambda gt recombinant clones by hybridization to single plaques in situ. Science 196:180–182

    Google Scholar 

  • Biggin MD, Gibson TJ, Hong GF (1983) Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci USA 80:3963–3965

    Google Scholar 

  • Borysiewcz L, Santor A, Evans D (1982) Renal failure in familial lecithin-cholesterol acyltransferase deficiency. J Med 204:411–426

    Google Scholar 

  • Castelli W, Doyle J, Gordon T, Hames C, Hulley S, Kagan A, McGee D, Vicic W, Zukel W (1977) HDL cholesterol and other lipids in coronary heart disease. Circulation 55:767–772

    Google Scholar 

  • Chen C, Albers J (1982) Characterization of proteoliposomes containing apoprotein A-1: a new substrate for the measurement of lecithin: cholesterol acyltransferase activity. J Lipid Res 23:680–691

    Google Scholar 

  • Chomczynsky P, Sacchi N (1987) Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Google Scholar 

  • Chung T, Abano DA, Fless GM, Scanu AM (1979) Isolation, properties and mechanism of in vitro action of LCAT from human plasma. J Biol Chem 254:7456–7464

    Google Scholar 

  • Cooper D (1983) Eukaryotic DNA methylation. Hum Genet 64:315–333

    Google Scholar 

  • Cooper D, Youssouflian H (1988) The CpG dinucleotide and human genetic disease. Hum Genet 78:151–155

    Google Scholar 

  • Doblasova M (1983) Lecithin: cholesterol aclytransferase and the regulation of endogenous cholesterol transport. Adv Lipid Res 10:107–194

    Google Scholar 

  • Fielding LJ, Fielding PE (1982) Cholesterol transport between cells and body fluids. Med Clin North Am 66:363–373

    Google Scholar 

  • Frohlich J, McLeod R (1986) Lecithin: cholesterol acyltransferase deficiency syndromes. In: Angel P, Frohlich J (eds) Hypoalpha-lipoproteinemia syndromes. lenum Press New York, pp 181–184

    Google Scholar 

  • Frohlich J, McLeod R, Pritchard H, Fesmire J, McConathy W (1988) Plasma lipoprotein abnormalities in heterozygotes for familial lecithin: cholesterol acyltransferase deficiency. Metabolism 37:3–8

    Google Scholar 

  • Gjone E, Norum KR, Glomset JA (1983) Familial lecithin-cholesterol acyltransferase deficiency. In: Stanbury JB, Wywgaarden JB, Fredrickson DS, Goldstein JS, Brown MS (eds) The metabolic basis of inherited disease. cGraw-Hill New York, pp 643–654

    Google Scholar 

  • Glomset JA (1968) The plasma lecithin: cholesterol acyltransferase reaction. J Lipid Res 9:155–170

    Google Scholar 

  • Godin D, Gray G, Frohlich J (1978) Erythrocyte membrane alterations in lecithin: cholesterol acyltransferase deficiency. Scand J Clin Lab Invest 21:327–329

    Google Scholar 

  • Gorman C, Moffat L, Howard B (1982) Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 2:1044–1051

    Google Scholar 

  • Hohn B, Murray K (1977) Packaging recombinant DNA molecules into bacteriophage particles in vitro. Proc Natl Acad Sci USA 74:3259–3262

    Google Scholar 

  • Humphries S, Chaves M, Tata F, Lima U, Owen J, Barysiewicz L, Catapanao A, Vergani C, Grjone E, Clemens M, Williamson R, McIntyre N (1988) A study of the structure of the gene for lecithin: cholesterol acyltransferase in four unrelated individuals with familial lecithin: cholesterol acyltransferase deficiency. Clin Sci 74:91–96

    Google Scholar 

  • Kannel W, Castelli W, Gordon T (1979) Cholesterol in the prediction of atherosclerotic disease. Ann Intern Med 90:85–90

    Google Scholar 

  • Lodish H (1988) Transport of secretary and membrane glycoproteins from the endoplasmic reticulum to the Golgi. J Biol Chem 263:2107–2110

    Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (eds) (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Cold Spring Harbor, NY

    Google Scholar 

  • McLean J, Fielding C, Dryna D, Dieplinger M, Baer B, Kohr W, Henlel W, Lawn R (1986) Cloning and expression of human lecithin: cholesterol acyltransferase cDNA. Proc Natl Acad Sci USA 83:2335–2339

    Google Scholar 

  • Mellon P, Parker V, Gluzman Y, Maniatis T (1981) Identification of DNA sequences required for transcription of the human α 1-globin gene in a new SV40 host-vector system. Cell 27:279–288

    Google Scholar 

  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR (1984) Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res 12:7035–7056

    Google Scholar 

  • Miura O, Hirosowa S, Kato A, Aoki N (1989) Molecular basis for congenital deficiency of α2-plasmid Inhibitor. J Clin Invest 83:1598–1604

    Google Scholar 

  • Norum KR, Gjone E (1967) Familial plasma lecithin cholesterol acyltransferase deficiency. Biochemical study of a new inborn error of metabolism. Scand J Clin Lab Invest 20:231–235

    Google Scholar 

  • Ross R (1986) The pathogenesis of atherosclerosis — an update. N Engl J Med 314:488–500

    Google Scholar 

  • Saiki RK, Gelfand DM, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491

    Google Scholar 

  • Selden R, Burke K, Rowe M, Godman H, More D (1986) Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol 6:3173–3179

    Google Scholar 

  • Vergani C, Catapano AL, Roma P, Giudici G (1984) A new case of familial LCAT deficiency. Acta Med Scand 214:173–176

    Google Scholar 

  • Wallentin L, Moberg B (1982) Lecithin: cholesterol acyltransfer rate and high density lipoprotein level in coronary artery disease. Atherosclerosis 41:155–165

    Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Genetica e di Biologia dei Microrganismi, Via Celoria, 26, I-20133, Milan, Italy

    Roberto Taramelli, Giulia Candiani & Sergio Ottolenghi

  2. Istituto Scientifico S. Raffaele, Via Olgettina, 60, I-20132, Milan, Italy

    Marco Pontoglio

  3. Institut für Medizinische Biologie der Universität, Schöpfstrasse 41, A-6020, Innsbruck, Austria

    Hans Dieplinger

  4. Istituto di Farmacologia, Via Balzaretti, 9, I-20129, Milan, Italy

    Alberico Catapano

  5. Department of Medicine, University of Washington, 326 Ninth Avenue, 98104-2499, Seattle, WA, USA

    John Albers

  6. Istituto di Semeiotica Medica, Via Pace, 14, I-20110, Milan, Italy

    Carlo Vergani

  7. Department of Cardiovascular Research, Genentech Inc., 460 Point San Bruno Boulevard, San Francisco, USA

    John McLean

Authors
  1. Roberto Taramelli
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  2. Marco Pontoglio
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  3. Giulia Candiani
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  4. Sergio Ottolenghi
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  5. Hans Dieplinger
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  6. Alberico Catapano
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  7. John Albers
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  8. Carlo Vergani
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  9. John McLean
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Taramelli, R., Pontoglio, M., Candiani, G. et al. Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele. Hum Genet 85, 195–199 (1990). https://doi.org/10.1007/BF00193195

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  • DOI: https://doi.org/10.1007/BF00193195

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