September 1, 1988Open Access
Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred.
Structured PICO
Do apo B gene mutations underlie hypobetalipoproteinemia in affected pedigrees?
P
Population
A large kindred (Idaho pedigree) with heterozygous hypobetalipoproteinemia.
I
Intervention
Linkage analysis of the apo B gene
O
Outcome
Cosegregation of the hypobetalipoproteinemia phenotype with a DNA haplotype of the apo B genesurrogate
Linkage analysis strongly suggests that apo B mutations underlie hypobetalipoproteinemia, demonstrating the utility of the candidate gene approach for metabolic disorders.
Abstract
Heterozygous hypobetalipoproteinemia is characterized by reduced plasma concentrations of LDL cholesterol, total triglycerides, and apo B to less than 50% of normal values. The molecular basis of this disorder remains unknown. The phenotype cosegregates with a DNA haplotype of the apo B gene in an Idaho pedigree, with a maximum decimal logarithm of the ratio (LOD) score of 7.56 at a recombination rate of zero. Individuals carrying this haplotype had total cholesterol levels of 96 mg/dl, LDL cholesterol levels of 37 mg/dl, triglycerides levels of 51 mg/dl, and apo B levels of 38 mg/dl. This study strongly suggests that apo B mutations underlie hypobetalipoproteinemia, and demonstrates the power of the candidate gene approach in linkage analysis for unraveling genetic determinants in metabolic disorders of undefined etiology.