Genetics of the low density lipoprotein receptor:

Six indices of low density lipoprotein (LDL) receptor activity were assayed in cultured fibroblasts from seven subjects with familial hypercholesterolemia (HC) and six subjects without HC (non‐HCs). Four non‐HCs, three HC heterozygotes and one HC homozygous proband belonged to one kindred (kindred A). The proband's fibroblast 125I‐LDL processing values fell within or were slightly above the range defined by fibroblasts from three “receptor‐negative” HC homozygotes. Thus, the plasma membrane receptor defect in this kindred is probably of the “receptor‐negative” category.LDL receptor‐dependent 125I‐LDL processing was about twice as high in fibroblasts from non‐HCs as in those from HC heterozygotes belonging to kindred A. The segregation pattern of LDL receptor activity in this kindred was compatible with control by a single gene locus. 12SI‐LDL processing values from non‐HCs, HC heterozygotes and HC homozygotes differed significantly from one another, but non‐HCs and HC heterozygotes showed some overlap. LDL receptor‐dependent 125I‐LDL association (plasma membrane binding plus intracellular accumulation) data for 6 HC heterozygous and 13 non‐HC fibroblast strains clustered into two a