Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1987 Mar;24(3):144–147. doi: 10.1136/jmg.24.3.144

Identification of deletions in the human low density lipoprotein receptor gene.

B Horsthemke, A Dunning, S Humphries
PMCID: PMC1049946  PMID: 3572996

Abstract

DNA samples from 70 unrelated UK patients with heterozygous familial hypercholesterolaemia were screened by Southern blot hybridisation with a 5' fragment of the human low density lipoprotein (LDL) receptor cDNA. In the majority of cases, the restriction fragment pattern of the LDL receptor gene was indistinguishable from that observed in normal subjects. However, three patients were found to have a deletion of approximately 1 kb in the central portion of the gene. Mapping experiments indicated that in two patients a similar deletion has occurred that includes all or part of exon 5, and in the third patient a deletion has occurred that includes exon 7. Taking into account our previously described patient with a deletion in the 3' part of the gene, this means that in four out of 70 UK patients with familial hypercholesterolaemia (6%), the defect is caused by a detectable deletion of part of the coding portion of the low density lipoprotein receptor gene.

Full text

PDF
144

Images in this article

145Image
on p.145
145Image
on p.145

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown M. S., Goldstein J. L. Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man. Science. 1974 Jul 5;185(4145):61–63. doi: 10.1126/science.185.4145.61. [DOI] [PubMed] [Google Scholar]
  2. Brown M. S., Goldstein J. L. Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Proc Natl Acad Sci U S A. 1974 Mar;71(3):788–792. doi: 10.1073/pnas.71.3.788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  4. Goldstein J. L., Schrott H. G., Hazzard W. R., Bierman E. L., Motulsky A. G. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest. 1973 Jul;52(7):1544–1568. doi: 10.1172/JCI107332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Horsthemke B., Kessling A. M., Seed M., Wynn V., Williamson R., Humphries S. E. Identification of a deletion in the low density lipoprotein (LDL) receptor gene in a patient with familial hypercholesterolaemia. Hum Genet. 1985;71(1):75–78. doi: 10.1007/BF00295672. [DOI] [PubMed] [Google Scholar]
  6. Humphries S. E., Donald J. A., McFadden J. J., Shull S., Williamson R., Jowett N. I., Galton D. J., Julsrud J. O., Berg K., Heiberg A. The use of polymorphic DNA and protein markers for the third complement component for determining linkage of familial hypercholesterolaemia. Atherosclerosis. 1984 Sep;52(3):267–278. doi: 10.1016/0021-9150(84)90056-x. [DOI] [PubMed] [Google Scholar]
  7. Humphries S. E., Kessling A. M., Horsthemke B., Donald J. A., Seed M., Jowett N., Holm M., Galton D. J., Wynn V., Williamson R. A common DNA polymorphism of the low-density lipoprotein (LDL) receptor gene and its use in diagnosis. Lancet. 1985 May 4;1(8436):1003–1005. doi: 10.1016/s0140-6736(85)91611-3. [DOI] [PubMed] [Google Scholar]
  8. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lehrman M. A., Goldstein J. L., Brown M. S., Russell D. W., Schneider W. J. Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain. Cell. 1985 Jul;41(3):735–743. doi: 10.1016/s0092-8674(85)80054-4. [DOI] [PubMed] [Google Scholar]
  10. Lehrman M. A., Russell D. W., Goldstein J. L., Brown M. S. Exon-Alu recombination deletes 5 kilobases from the low density lipoprotein receptor gene, producing a null phenotype in familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3679–3683. doi: 10.1073/pnas.83.11.3679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lehrman M. A., Schneider W. J., Südhof T. C., Brown M. S., Goldstein J. L., Russell D. W. Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985 Jan 11;227(4683):140–146. doi: 10.1126/science.3155573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES