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Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing Mutations
- Anouk van der Graaf, MD;
- Sigrid W. Fouchier, PhD;
- Maud N. Vissers, PhD;
- Joep C. Defesche, PhD;
- Albert Wiegman, MD, PhD;
- Raaj R. Sankatsing, MD;
- Barbara A. Hutten, PhD;
- Mieke D. Trip, MD, PhD; and
- John J.P. Kastelein, MD, PhD
- From Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands.
Background: Some hereditary disorders of lipoprotein metabolism can be characterized by hyper- as well as hypocholesterolemia. We describe a family in which 2 counteracting mutations in the apolipoprotein B gene (APOB) were transmitted and resulted in a clinically normolipidemic phenotype.
Case Report: A 38-year-old man (index patient [patient II-4 in Figure]) and 2 of his children (patients III-1 and III-3) had elevated levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB) caused by a point mutation (R3500Q) in APOB, underlying familial defective apolipoprotein B (FDB). In contrast, his spouse (patient II-3) and a third child (patient III-4) had substantially low levels of LDL cholesterol, apolipoprotein B (apoB), and triglycerides caused by another mutation (11712delC) in APOB, leading to familial hypobetalipoproteinemia (FHBL) (1). A fourth child (patient III-2) had a normal lipoprotein profile. DNA analysis revealed that this child carried the R3500Q mutation on 1 allele and the 11712delC mutation on the other allele and, …
