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

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.

• Authors: M Leppert, J L Breslow, L Wu, S Hasstedt, P O'Connell, M Lathrop, R R Williams, R White, J M Lalouel
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 82 Issue 3 Pg. 847-51 (Sep 1988) ISSN: 0021-9738 [Print] United States
• PMID: 2901434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoproteins B
• Lipids

Topics

• Adolescent
• Adult
• Aged
• Analysis of Variance
• Apolipoproteins B (blood, deficiency, genetics)
• Child
• Female
• Genetic Linkage
• Haplotypes
• Humans
• Hypobetalipoproteinemias (blood, genetics)
• Hypolipoproteinemias (genetics)
• Lipids (blood, genetics)
• Male
• Middle Aged
• Mutation
• Nuclear Family
• Pedigree
• Polymorphism, Restriction Fragment Length