Phenotypic characterization of a patient homozygous for the D558N LDL receptor gene mutation.
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.
Jensen
H K
HK
Center for Medical Molecular Biology, Aarhus University Hospital, Denmark. hkj@aas.arhusamt.dk
Jensen
L G
LG
Heath
F
F
Melsen
F
F
Hansen
P S
PS
Meinertz
H
H
Bolund
L
L
Gregersen
N
N
Faergeman
O
O
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*
D011973:Receptors, LDL