Evidence for a third genetic locus causing familial hypercholesterolemia: A non-LDLR, non-APOB kindred

Journal of Lipid Research

Volumn 40, Issue 6, 1999, Pages 1113-1122

  Haddad, L ^a,b,d,e   Day, I N M ^a,b,d,f   Hunt, S ^b,c,d   Williams, R R ^b,c,d   Humphries, S E ^a,b,d   Hopkins, P N ^b,c,d  

^a Centre for Cardiovascular Genetics   (United Kingdom)

^b ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^c Cardiovascular Genetics   (United States)

^d UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^e IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

^f UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

APOB gene; Familial hypercholesterolemia; LDLR gene; Microsatellites

Indexed keywords

APOLIPOPROTEIN B; LOW DENSITY LIPOPROTEIN; MICROSATELLITE DNA; VERY LOW DENSITY LIPOPROTEIN;

ARTICLE; FAMILIAL DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; GENE FREQUENCY; GENE LOCUS; GENE MUTATION; GENETIC ANALYSIS; GENETIC LINKAGE; HUMAN; PHENOTYPE; PRIORITY JOURNAL; SINGLE STRAND CONFORMATION POLYMORPHISM;

EID: 0033058362     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (50)

1. Goldstein, J. L., and M. S. Brown. 1989. Familial hypercholesterolemia. In C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, editors. The Metabolic Basis of Inherited Disease. McGraw-Hill, New York. 1215-1250.
2. Hobbs, H. H., M. S. Brown, and J. L. Goldstein. 1992. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum. Mutat. 1: 445-466.
3. Day, I. N. M., R. A. Whittall, S. D. O'Dell, L. Haddad, M. K. Bolla, V. Gudnason, and S. E. Humphries. 1997. Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolemia. Hum. Mutat. 10: 116-127.
4. Vega, G. L., and S. M. Grundy. 1986. In vitro evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolemia. J. Clin. Invest. 78: 1410-1414.
5. Innerarity, T. L., R. W. Mahley, K. H. Weisgraber, T. P. Bersot, R. M. Krauss, G. L. Vega, S. M. Grundy, W. Fried, J. Davignon, and B. J. McCarthy. 1990. Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia. J. Lipid Res. 31: 1337-1349.
6. Myant, N. B. 1993. Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolemia. Atherosclerosis. 104: 1-18.
7. Pullinger, C. R., L. K. Hennessy, J. E. Chatterton, W. Liu, J. A. Love, C. M. Mendel, P. H. Frost, J. M. Malloy, V. N. Schumaker, and J. P. Kane. 1995. Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity. J. Clin. Invent. 95: 1225-1234.
8. Gaffney, D., J. M. Read, I. M. Cameron, K. Vass, M. J. Caslake, J. Shepard, and C. J. Packard. 1995. Independent mutations at the codon 3500 of the apolipoprotein B gene are associated with hyperlipidemia. Arterioscler. Thromb. Vasc. Biol. 15: 1025-1029.
9. Ludwig, E. H., P. N. Hopkins, A. Allen, L. L. Wu, R. R. Williams, J. L. Anderson, R. H. Ward, J-M. Lalouel, and T. L. Innerarity. 1997. Association of genetic variations in apolipoprotein B with hypercholesterolemia, coronary artery disease, and receptor binding of low density lipoproteins. J. Lipid Res. 38: 1361-1373.
10. Sun, X. M., D. D. Patel, B. L. Knight, and A. K. Soutar, with the FH Regression Study Group. 1997. Comparison of the genetic defect with LDL receptor activity in cultured cells from patients with a clinical diagnosis of heterozygous FH. Arterioscl. Thromb. Vasc. Biol. 17: 3092-3101.
11. Myant, N. B., and J. Slack. 1976. Type II-hyperlipoproteinaemia. In G. Schettler, H. Greten, G. Schlierf, and D. Seidel, editors. Handbuch der inneren Medizin: Fettstoffwechsel. Springer-Verlag, Berlin. 275-300.
12. Marz, W., M. W. Baumstark, H. Scharnagl, V. Ruzicka, S. Buxbaum, J. Herwig, T. Pohl, A. Russ, L. Schaaf, A. Berg, H. J. Bohles, K. H. Usadel, and W. Gross. 1993. Accumulation of 'small dense' low density lipoproteins in a homozygous patient with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL-subfractions with the LDL receptor. J. Clin. Invest. 92: 2922-2933.
13. Gallagher, J. J., and N. B. Myant. 1995. The affinity of low-density lipoprotein remnants for the low-density lipoprotein receptor in homozygous familial defective apolipoprotein B-100. Atherosclerosis. 115: 263-272.
14. Uauy, R., G. L. Vega, and S. M. Grundy. 1991. Coinheritance of two mild defects in low density lipoprotein receptor function produces severe hypercholesterolemia. J. Clin. Endocrin. Metab. 72: 179-187.
15. Koivisto, P. V. I., U. M. Koivisto, P. T. Kovanen, H. Gylling, T. A. Miettinen, and K. Kontula. 1993. Deletion of exon 15 of the LDL receptor gene is associated with a mild form of familial hypercholesterolaemia. Arterioscler. Thromb. 13: 1680-1688.
16. Moorjani, S., M. Roy, A. Torres, C. Betard, C. Gagne, M. Lambert, D. Brun, J. Davignon, and P. Lupien. 1993. Mutations of low-density-lipoprotein-receplor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hyper-cholesterolaemia. Lancet. 341: 1303-1306.
17. Emi, M., R. M. Hegele, P. N. Hopkins, L. L. Wu, R. Plaetke, R. R. Williams, and J. M. Lalouel. 1991. Effects of three genetic loci in a pedigree with multiple lipoprotein phenotypes. Arteriosclerosis. 11: 1349-1355.
18. Sirtori, C. R., A. L. Catapano, G. Franceschini, A. Corsini, G. Noseda, C. Fragiacomo, E. Panzeri, V. Vaccarino, S. Guenzi, G. Casari, and S. Baralle. 1991. Aortic and coronary atheromatosis in a woman with severe hypercholesterolemia without LDL receptor alterations. Eur. Heart. J. 12: 818-824.
19. Miserez, A. R., H. Schuster, N. Chiodetti, and U. Keller. 1994. Polymorphic haplotypes and recombination rates at the LDL receptor gene locus in subjects with and without familial hypercholesterolemia who are from different populations. Am. J. Hum. Genet. 52: 808-826.
20. Kingsley, D. M., and M. Krieger. 1984. Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity. Proc. Natl. Acad. Sci. USA. 81: 5454-5458.
21. Haddad, L., L. B. Day, J. Attwood, S. Povey, S. E. Humphries, and I. N. M. Day. 1997. Development of a microsatellite-based approach to co-segregation analysis of familial hypercholesterolaemic kindreds. Ann. Hum. Genet. 61: 497-506.
22. Ashworth, L. K., M. A. Batzer, B. Brandriff, E. Branscomb, P. de Jong, E. Garcia, J. A. Garnes, L. A. Gordon, J. E. Lamerdin, G. Lennon, H. Mohrenweiser, A. A. Olsen, T. Selzak, and A. V. Carrano. 1995. An integrated metric physical map of chromosome 19. Nat. Genet. 11: 422-427.
23. Day, I. N. M., L. Haddad, S. D. O'Dell, L. B. Day, R. Whittall, and S. Humphries. 1997. Identification of a common low density lipoprotein receptor mutation (R329X) in the South of England: complete linkage disequilibrium with an allele of microsatellite D19S394. J. Med. Genet. 34: 111-116.
24. Zuliani, G., and H. H. Hobbs. 1990. Tetranucleotide repeat polymorphism in the apolipoprotein B gene. Nucliec Acids Res. 18: 4299.
25. Boerwinkle, E., W. Xiong, E. Fourest, and L. Chan. 1988. Rapid typing of tandemly repeated hypervariable loci by the polymerase chain reaction: application to the apolipoprotein B 3′ hypervariable region. Proc. Natl. Acad. Sci. USA. 85: 1462-1466.
26. Buetow, K. H., J. L. Weber, L. Ludwigsen, T. Scherpbier-Heddema, G. M. Duyk, V. C. Sheffield, Z. Wang, and J. C. Murray. 1994. Integrated human genome-wide maps constructed using the CEPH reference panel. Nat. Genet. 6: 391-393.
27. Williams, R. R., S. J. Hasstedt, D. E. Wilson, K. O. Ash, F. G. Yanowitz, G. E. Reiber, and H. Kuida. 1986. Evidence that men with familial hypercholesterolemia can avoid early coronary death: an analysis of 77 gene carriers in four Utah pedigrees. J. Am. Med. Assor. 255: 219-224.
28. Williams, R. R., and S. C. Hunt. 1987. Recruitment of members of high-risk Utah pedigrees. Controlled Clin. Trials. 8: 105S-114S.
29. Williams, R. R., S. C. Hunt, M. C. Schumacher, R. A. Hegele, M. F. Leppert, E. H. Ludwig, and P. N. Hopkins. 1993. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am. J. Cordial. 72: 171-176.
30. Williams, R. R., I. Hamilton-Craig, G. M. Kostner, R. A. Hegele, M. R. Hayden, S. N. Pimstone, O. Faergeman, H. E. S-T. Schuster, U. Beisiegel, C. Keller, A. E. Czeizel, E. Leitersdorf, J. C. Kastelein, J. J. P. Defesche, L. Ose, T. P. Leren, H. C. Seftel, F. J. Raal, A. D. Marais, M. Eriksson, U. Keller, A. R. Miserez, T. Jeck, D. J. Betterridge, S. E. Humphries, I. N. M. Day, P. L. Kwiterovich, R. S. Lees, E. Stein, R. Illingworth, J. Kane, and V. Boulyjenkov. 1996. MED-PED: An integrated genetic strategy for preventing early deaths. In Genetic Approaches to Noncommunicable Diseases. K. Berg, V. Boulyjenkov, and Y. Christen, editors. Springer-Verlag Heidelberg. 35-45.
31. Williams, R. R., S. C. Hunt, G. K. Barlow, R. M. Chamberlain, A. D. Weinberg, H. P. Cooper, J. P. Carbonari, and A. M. Gotto. 1988. Health Family Trees: a tool for finding and helping young family members of coronary and cancer prone pedigrees in Texas and Utah. Am. J. Pub. Health. 78: 1283-1286.
32. Williams, R. R., M. C. Schumacher, G. K. Barlow, S. C. Hunt, J. L. Ware, M. Pratt, and B. D. Latham. 1993. Documented need for more effective diagnosis and treatment of familial hypercholesterolemia according to data from 502 heterozygotes in Utah. Am. J. Cardiol. 72: 18D-24D.
33. Leppert, M. F., S. J. Hasstedt, T. Holm, P. O'Connell, L. L. Wu, K. O. Ash, R. R. Williams, and R. L. White. 1986. A DNA probe for the LDL receptor gene is tightly linked to hypercholesterolemia in a pedigree with early coronary disease. Am. J. Hum. Genet. 39: 300-306.
34. Hobbs, H. H., D. W. Russell, M. S. Brown, and J. L. Goldstein. 1990. The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein. Annu. Rev. Genet. 24: 133-170.
35. Lipid Research Clinics Program Manual of Laboratory Operations. 1974. DHEW (NIH) Publication No. 75-628.
36. Wu, L. L., G. R. Warnick, J. T. Wu., R. R. Williams, and J. M. Lalouel. 1989. A rapid micro-scale procedure for determination of total lipid profile. Clin. Chem. 35: 1486-1491.
37. Kunkel, L. M., K. D. Smith, S. H. Boyer, D. S. Borgaonkar, S. S. Wachtel, O. J. Miller, W. R. Breg, H. W. Jones, and J. M. Rary. 1977. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc. Natl. Acad, Sci. USA. 74: 1245-1249.
38. Laywood, A., R. Whittall, V. Gudnason, S. E. Humphries, and I. N. M. Day. 1994. Handling of large (300 × 400 mm), thin (0.4 mm) polyacrylamide gels and recovery as dried gels. Biotechniques. 17: 850-854.
39. Marz, W., V. Ruzicka, E. Fisher, A. P. Russ, W. Schneider, and W. Grob. 1993. Typing of the 3′ hypervariable region of the apolipoprotein gene: approaches, pitfalls, and applications. Electrophoresis. 14: 169-173.
40. Mamotte, C. D. S., and F. M. van Bockxmeer. 1993. A robust strategy for screening and confirmation of familial defective apolipoprotein B-100. Clin. Chem. 39: 118-121.
41. Day, I. N. M., and S. E. Humphries. 1994. Electrophoresis for genotyping: microtitre array diagonal gel electrophoresis (MADGE) on horizontal polyacrylamide (H-PAGE) gels, Hydrolink or agarose. Anal. Biochem. 222: 389-395.
42. Wu, L. H., J. T. Wu, and P. N. Hopkins. 1994. Apolipoprotein E. Laboratory determination and clinical significance. In N. Rifai and G. R. Warnick, editors. Laboratory Measurement of Lipids, Lipoproteins and Apolipoproteins. AACC Press, Washington, DC. 279-305.
43. Liu, Q., and S. S. Sommer. 1994. Parameters affecting the sensitivities of dideoxy fingerprinting and SSCP. PCR Methods. Appl. 4: 97-108.
44. Sun, X. M., J. C. Webb, V. Gudnason, S. Humphries, M. Seed, G. R. Thompson, B. L. Knight, and A. K. Soutar. 1992. Characterization of deletions in the LDL receptor gene in patients with familial hypercholesterolemia in the United Kingdom. Arterioscler. Thromb. 12: 762-770.
45. Krawczak, M., J. Reiss, and D. N. Cooper. 1992. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet. 90: 41-54.
46. Leren, T. P., K. Solberg, O. K. Rodningen, S. Tonstad, and K. Berg. 1994. Two founder mutations in the LDL receptor gene in Norwegian familial hypercholesterolaemia subjects. Atherosclerosis. 111: 175-182.
47. Ward, A. J., M. O'Kane, I. Young, D. P. Nicholls, N. C. Nevin, and C. A. Graham. 1995. Three novel mutations in the EGF precursor homology domain of the low-density lipoprotein receptor gene in Northern Irish patients with familial hypercholesterolaemia. Hum. Mutat. 6: 254-256.
48. Kotze, M. J., E. Langenhoven, L. Warnich, M. P. Marx, and A. E. Retief. 1989. Molecular characterisation of a low frequency mutation in exon 8 of the low-density lipoprotein receptor gene. S. Afr. Med. J. 76: 402-405.
49. Solberg, K., O. K. Rodningen, S. Tonstad, L. Ose, and T. P. Leren. 1994. Familial hypercholesterolaemia caused by a non-sense mutation in codon 329 of the LDL receptor gene. Scand. J. Clin. Lab. Invest. 54: 605-609.
50. Tricot-Guerber, F., B. Sainjore, K. Valenti, T. Foulon, M. Bost, and A. J. Hadjian. 1995. Identification of a mutation, N543H, in exon 11 of the low-density lipoprotein receptor gene in a French family with familial hypercholesterolaemia. Hum. Mutat. 6: 87-88.