Molecular genetics of the LDL receptor gene in familial hypercholesterolemia

  title={Molecular genetics of the LDL receptor gene in familial hypercholesterolemia},
  author={Helen H. Hobbs and Michael S. Brown and Joseph L. Goldstein},
  journal={Human Mutation},
The low density lipoprotein (LDL) receptor is a cell surface transmembrane protein that mediates the uptake and lysosomal degradation of plasma LDL, thereby providing cholesterol to cells. Mutations disrupting the function of this receptor produce autosomal dominant familial hypercholesterolemia (FH). Affected individuals have elevated plasma levels of LDL, which causes premature coronary atherosclerosis. To date, 71 mutations in the LDL receptor gene have been characterized at a molecular… 

[Research progression of LDLR mutations in Chinese Familial hypercholesterolemia].

This review provides a comprehensive overview of LDLR gene mutations in Chinese FH patients and identifies 108 variants that should be considered for FH diagnosis and therapy.

The Major Molecular Causes of Familial Hypercholesterolemia

The molecular disorder in LDLR, ApoB-100, LDLRAP1 and PCSK gene is highlighted, leading to the possible accession on early diagnosis, screening of FH based on the clinical characteristics, family history, evaluated LDL-Cholesterol levels and recently genetic testing aided, hence molecular based therapy will be applied or recommended to FH patients.

Software and database for the analysis of mutations in the human LDL receptor gene

To facilitate the mutationalAnalysis of the LDLR gene, and promote the analysis of the relationship between genotype and phenotype, a software package along with a computerized database have been created.

Molecular basis of familial hypercholesterolemia: An Indian experience

The findings warrant application of a generalized mutation screening method in search for new LDL receptor gene defects, which have occurred at CpG dinucleotide, a mutational hotspot in human genetic disease.

Two novel point mutations in the EGF precursor homology domain of the LDL receptor gene causing familial hypercholesterolemia

Analysis of single-strand conformation polymorphisms of exons 10 and 11 of the LDL receptor gene from familial hypercholesterolemia heterozygotes indicated the presence of two mutations, which were characterized by DNA sequencing.

LDL‐receptor mutations in Europe

This work focuses on the published European LDLR mutation data that reflect its heterogeneity and phenotypic penetrance and emphasizes the crucial importance of LDL metabolism intra‐ and extracellularly in determining LDL‐cholesterol serum concentration.

Clinical Expression of Familial Hypercholesterolemia in Clusters of Mutations of the LDL Receptor Gene That Cause a Receptor-Defective or Receptor-Negative Phenotype

Haplotype analysis showed that all families of the major clusters shared the same intragenic haplotype cosegregating with the mutation, thus suggesting the presence of common ancestors.

Genetic Basis for Diagnosis of Novel Mutation of LDLReceptor Gene

The molecular analysis of low density lipoprotein for diagnosis of familial hypercholesterolemia, an autosomal dominant disease caused by a multitude of LDL receptor (LDLR) gene mutations and confirmation of these mutations by DNA sequencing were confirmed.



DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia

DNA samples from 25 unrelated Danish patients with familial hypercholesterolemia were screened by Southern blot hybridization to detect gross alterations in the low density lipoprotein (LDL) receptor gene and three patients were found to have a deletion, which seems to support a notion of recombination hot spots which involve Alusequences.

Characterization of six partial deletions in the low-density-lipoprotein (LDL) receptor gene causing familial hypercholesterolemia (FH).

There appear to be preferential sites within the LDL receptor gene for major rearrangements resulting in deletions, suggesting that molecular heterogeneity underlies the molecular pathology of FH.

The LDL receptor in familial hypercholesterolemia: use of human mutations to dissect a membrane protein.

The analysis of four large deletions has revealed an unexpectedly universal involvement of Alu repeats in their generation, and studies indicate that repetitive DNAs can destabilize a gene through homologous recombination.

Clinical studies in a kindred with a kinetic LDL receptor mutation causing familial hypercholesterolemia.

We have studied a family carrying a variant of the class 2 mutation of familial hypercholesterolemia (FH) in which there is unusual longevity and in which obligate heterozygotes did not express

Evidence for a dominant gene that suppresses hypercholesterolemia in a family with defective low density lipoprotein receptors.

An unusual kindred with familial hypercholesterolemia in which one-third of the relatives with a mutant LDL receptor gene have normal plasma cholesterol concentrations is described, which may explain the occasional observation of normal LDL-cholesterol concentrations in heterozygotes for LDL receptor mutations.

New Variant of Low Density Lipoprotein Receptor Gene: FH×Tonami

A new variant of the low density lipoprotein receptor (LDLR) gene was ascertained through Southern biotting analysis fof LDLR genes of 35 unrelated Japanese patients with heterozygous familial

Characterization of deletions in the LDL receptor gene in patients with familial hypercholesterolemia in the United Kingdom.

  • X. SunJ. Webb A. Soutar
  • Biology, Medicine
    Arteriosclerosis and thrombosis : a journal of vascular biology
  • 1992
A sample of 200 patients with a clinical diagnosis of heterozygous (189) or homozygous (11) familial hypercholesterolemia (FH) attending lipid clinics in the London area have been screened for the

Analysis of a recycling-impaired mutant of low density lipoprotein receptor in familial hypercholesterolemia.

A mutant low density lipoprotein (LDL) receptor with abnormal ligand binding and recycling abilities was found in a patient with familial hypercholesterolemia, found to be present on the cell surface because the mature form was susceptible to Pronase digestion, and specific monoclonal antibody against the LDL receptor (IgG-C7) could bind to the cellsurface.

The identification of two low-density lipoprotein receptor gene mutations in South African familial hypercholesterolaemia.

Restriction enzyme analysis of PCR-amplified DNA from blood and tissue samples now permits accurate diagnosis of point mutations in low-density lipoprotein genes of patients with familial hypercholesterolaemia.