Figure 5. .

Pedigree of a 32-year-old African American woman (II.2) who is compound heterozygous for loss-of-function mutations in PCSK9. A, The proband (I.2) of the family is a participant in the Dallas Heart Study¹⁹ who was found to be heterozygous for the Y142X allele in PCSK9. Fasting blood samples were obtained from additional family members. Plasma and serum were isolated, and the lipids and lipoprotein levels were measured using commercial reagents (table 1). The LDL-C and age- and sex-adjusted percentiles are provided for each family member. PCSK9 was immunoprecipitated from the plasma of selected family members with use of a polyclonal anti-PCSK9 antibody (295A), was size-fractionated by SDS-PAGE, and then was immunoblotted as described in the “Material and Methods” section. Individual II.3 was sampled, but the analysis of circulating PCSK9 was not performed on this subject. B, PCSK9-WT (WT) and mutant PCSK9 (ΔR97) were expressed in HEK-293 cells. After 2 d, the cell lysates and the medium were collected and subjected to immunoblotting as described in the figure 1 legend. NA = not available; P = precursor; M = mature; S = secreted.