Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred.
Open Access
- 1 September 1988
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 82 (3) , 847-851
- https://doi.org/10.1172/JCI113688
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.Keywords
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