Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor.
Cultured amniotic-fluid cells from a fetus at risk for homozygous familial hypercholesterolaemia (F.H.) almost completely lacked cell-surface receptors for plasma low-density lipoprotein (L.D.L.), as evidenced by direct measurement of binding, uptake, and degradation of 125I-L.D.L.Functional consequences of L.D.L. binding to the receptor--i.e., suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and stimulation of cholesterol esterification--were proportionately reduced when compared with results in cultured amniotic cells from two control fetuses.
In one patient with homozygous familial hypercholesterolemia whose cells fail to bind 125I-labeled IgG-C7, no immunoreactive LDL receptor spot was detected after electrophoresis.
A Japanese subject with homozygous familial hypercholesterolemia was found to have a 7.8-kilobase deletion in the gene for the low density lipoprotein receptor.
The Lebanese allele at the low density lipoprotein receptor locus. Nonsense mutation produces truncated receptor that is retained in endoplasmic reticulum.
A previous study of the low density lipoprotein (LDL) receptor gene haplotype distribution in 12 unrelated South African patients with homozygous familial hypercholesterolaemia indicated the existence of several different receptor gene mutations in this patient pool.
The LDL receptor mutations in Japanese FH were heterogeneous and included defects in synthesis, post-translational processing, ligand-binding activity, and internalization of the LDL receptor.
The low density lipoprotein (LDL) receptors in fibroblasts from 132 subjects with the clinical syndrome of homozygous familial hypercholesterolemia were analyzed by immunoprecipitation with an anti-LDL receptor monoclonal antibody.
Ten restriction fragment length polymorphisms of the LDL receptor gene were used for haplotype analysis in 12 unrelated patients with homozygous familial hypercholesterolemia.
Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors.
Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors.
We describe here a naturally occurring mutant LDL receptor, found in a patient with homozygous familial hypercholesterolaemia, which lacks the first two growth-factor-like repeats of the EGF-precursor-like ('homology') domain.