Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001055:Apolipoproteins B / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D002648:Child; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000235:genetics*; D007009:Hypolipoproteinemias / Q000235:genetics*; D008055:Lipids / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009679:Nuclear Family; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D001055:Apolipoproteins B; D008055:Lipids