Arteriosclerosis and Thrombosis, Vol 13, 1680-1688, Copyright © 1993 by American Heart Association

ARTICLES

Deletion of exon 15 of the LDL receptor gene is associated with a mild form of familial hypercholesterolemia. FH-Espoo

PV Koivisto, UM Koivisto, PT Kovanen, H Gylling, TA Miettinen and K Kontula
Second Department of Medicine, University of Helsinki, Finland.

We describe a mutation of the low-density lipoprotein (LDL) receptor gene, designated familial hypercholesterolemia (FH)-Espoo, which deletes exon 15 of the LDL receptor gene. The mutant receptor is predicted to lack 57 amino acids, including 18 serine and threonine residues, which are the sites of the clustered O-linked sugars of the receptor. Studies on 10 carriers of this gene revealed that FH-Espoo is associated with an exceptionally mild form of FH. Thus, in conditions in which cell proliferation was rendered dependent on the function of LDL receptors, lymphocytes from the patients with the FH-Espoo allele had a growth rate intermediate between those from healthy subjects and patients with the FH-Helsinki gene, a mutation known to abolish LDL receptor function. The in vivo fractional catabolic rate of LDL apolipoprotein B was lower than normal in the two FH-Espoo heterozygotes studied. Although higher than those in healthy controls, the serum LDL cholesterol concentrations in patients with the FH-Espoo gene were significantly lower than those in patients with the FH- Helsinki mutation. The thickness of the Achilles tendons was within the normal limits in subjects with the FH-Espoo gene. Our study suggests that moderate varieties of hypercholesterolemia, ie, those not considered to represent FH, may occasionally be due to subtle LDL receptor gene mutations.

This article has been cited by other articles:

				M. A. Austin, C. M. Hutter, R. L. Zimmern, and S. E. Humphries Familial Hypercholesterolemia and Coronary Heart Disease: A HuGE Association Review Am. J. Epidemiol., September 1, 2004; 160(5): 421 - 429. [Abstract] [Full Text] [PDF]

				K. E HEATH, R. A WHITTALL, G. J MILLER, and S. E HUMPHRIES I705 variant in the low density lipoprotein receptor gene has no effect on plasma cholesterol levels J. Med. Genet., September 1, 2000; 37(9): 713 - 715. [Full Text]

				K. E Heath, I. N M Day, and S. E Humphries Universal primer quantitative fluorescent multiplex (UPQFM) PCR: a method to detect major and minor rearrangements of the low density lipoprotein receptor gene J. Med. Genet., April 1, 2000; 37(4): 272 - 280. [Abstract] [Full Text]

				L. Haddad, I. N. M. Day, S. Hunt, R. R. Williams, S. E. Humphries, and P. N. Hopkins Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred J. Lipid Res., June 1, 1999; 40(6): 1113 - 1122. [Abstract] [Full Text]

				X.-M. Sun, D. D. Patel, B. L. Knight, and A. K. Soutar Comparison of the Genetic Defect with LDL-Receptor Activity in Cultured Cells from Patients With a Clinical Diagnosis of Heterozygous Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3092 - 3101. [Abstract] [Full Text]

				A. F. Vuorio, H. Turtola, and K. Kontula Neonatal Diagnosis of Familial Hypercholesterolemia in Newborns Born to a Parent With a Molecularly Defined Heterozygous Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3332 - 3337. [Abstract] [Full Text]

				U.-M. Koivisto, H. Gylling, T. A. Miettinen, and K. Kontula Familial Moderate Hypercholesterolemia Caused by Asp235->Glu Mutation of the LDL Receptor Gene and Co-occurrence of a De Novo Deletion of the LDL Receptor Gene in the Same Family Arterioscler Thromb Vasc Biol, July 1, 1997; 17(7): 1392 - 1399. [Abstract] [Full Text]

				H. Bujo, K. A. Lindstedt, M. Hermann, L. M. Dalmau, J. Nimpf, and W. J. Schneider Chicken Oocytes and Somatic Cells Express Different Splice Variants of a Multifunctional Receptor J. Biol. Chem., October 6, 1995; 270(40): 23546 - 23551. [Abstract] [Full Text] [PDF]

				J. Ferrieres, J. Lambert, S. Lussier-Cacan, and J. Davignon Coronary Artery Disease in Heterozygous Familial Hypercholesterolemia Patients With the Same LDL Receptor Gene Mutation Circulation, August 1, 1995; 92(3): 290 - 295. [Abstract] [Full Text]

				H. Nissen, A. B. Hansen, P. Guldberg, N. E. Petersen, M. L. Larsen, T. Haghfelt, K. Kristiansen, and M. Horder Genetic Diagnosis With the Denaturing Gradient Gel Electrophoresis Technique Improves Diagnostic Precision in Familial Hypercholesterolemia Circulation, March 15, 1995; 91(6): 1641 - 1646. [Abstract] [Full Text]