In 1979 Steinberg and colleagues recognized a unique kindred with normotriglyceridemic
hypobetalipoproteinemia (1979. J. Clin. Invest. 64:292-301). We have undertaken an intensive reexamination of this kindred and have studied 41 family members in three generations. In this family we document the presence of two distinct
apo B alleles associated with low plasma concentrations of
apolipoprotein (
apo) B and
low density lipoprotein (
LDL) cholesterol and we trace the inheritance of these two alleles over three generations. One of the alleles resulted in the production of an abnormal, truncated
apo B species,
apo B-37. The other
apo B allele was associated with reduced plasma concentrations of the normal
apo B species,
apo B-100. H.J.B., the proband, and two of his siblings had both abnormal
apo B alleles and were therefore compound heterozygotes for
familial hypobetalipoproteinemia. Their average
LDL-cholesterol level was 6 +/- 9 mg/dl. All of the offspring of the three compound heterozygotes had
hypobetalipoproteinemia, and each had evidence of only one of the abnormal
apo B alleles. In the entire kindred, we identified six heterozygotes for
familial hypobetalipoproteinemia who had only the abnormal
apo B-37 allele and their average
LDL cholesterol was 31 +/- 12 mg/dl. We identified 10 heterozygotes who had only the allele for reduced plasma concentrations of
apo B-100 and their
LDL cholesterol level was 31 +/- 15 mg/dl. Unaffected family members (n = 22) had
LDL cholesterol levels of 110 +/- 27 mg/dl. This report describes the first kindred in which two distinct abnormal
apo B alleles have been identified, both of which are associated with
familial hypobetalipoproteinemia.