Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred.

M Leppert; J L Breslow; L Wu; S Hasstedt; P O'Connell; M Lathrop; R R Williams; R White; J M Lalouel

doi:10.1172/JCI113688

Howard Hughes Medical Institute, University of Utah Medical Center, Salt Lake City 84132.

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Published in Volume 82, Issue 3 on September 1, 1988
J Clin Invest. 1988;82(3):847–851. https://doi.org/10.1172/JCI113688.
© 1988 The American Society for Clinical Investigation

Published September 1, 1988 - Version history

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.

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