title: Phenotypic characterization of a patient homozygous for the D558N LDL receptor gene mutation.
abstract: We describe the clinical, biochemical, and genetic features of a patient with true homozygous familial hypercholesterolemia due to the D558N low-density lipoprotein receptor gene mutation, previously designated FH Cincinnati-4. Functional flow-cytometric analysis of the LDL receptorR protein on upregulated EBV-transformed lymphocytes indicated reduction of the number of receptors on the cell surface by 87% and reduction of receptor activity by 89% compared to control cells. With drugs and a portacaval shunt operation, performed when the patient was 15 years old, serum cholesterol was reduced from about 28 to about 15 mmol/l. He died at the age of 32 of a myocardial infarction. The autopsy showed generalized atherosclerosis, especially in the coronary arteries, which were severely stenosed proximally. A rare finding was a large intracranial xanthoma that apparently had been asymptomatic.
authors.affiliation: Center for Medical Molecular Biology, Aarhus University Hospital, Denmark. hkj@aas.arhusamt.dk
authors.forename: H K
authors.initials: HK
authors.lastname: Jensen
authors.forename: L G
authors.initials: LG
authors.lastname: Jensen
authors.forename: F
authors.initials: F
authors.lastname: Heath
authors.forename: F
authors.initials: F
authors.lastname: Melsen
authors.forename: P S
authors.initials: PS
authors.lastname: Hansen
authors.forename: H
authors.initials: H
authors.lastname: Meinertz
authors.forename: L
authors.initials: L
authors.lastname: Bolund
authors.forename: N
authors.initials: N
authors.lastname: Gregersen
authors.forename: O
authors.initials: O
authors.lastname: Faergeman
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002895:Chromosomes, Human, Pair 5; D005091:Exons; D005500:Follow-Up Studies; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009154:Mutation; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL