Association between a Specific Apolipoprotein B Mutation and Familial Defective Apolipoprotein B-100

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 2; pp. 587 - 591
• Main Authors: Soria, Luis F., Ludwig, Erwin H., Howard R. G. Clarke, Vega, Gloria L., Grundy, Scott M., McCarthy, Brian J.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1989; National Acad Sciences
• Subjects: 550401 - Genetics- Tracer Techniques; Alleles; Amino Acid Sequence; Amino acids; APOLIPOPROTEINS; Apolipoproteins B - genetics; Base Sequence; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BLOOD CHEMISTRY; CHOLESTEROL; Cloning, Molecular; CODONS; DAYS LIVING RADIOISOTOPES; DISEASES; Disorders of blood lipids. Hyperlipoproteinemia; DNA; DNA - genetics; DNA BASE TRANSITIONS; DNA SEQUENCING; ETIOLOGY; Exons; GENE MUTATIONS; Genetic mutation; Genetic Vectors; Genotype; Haplotypes; HEREDITARY DISEASES; Humans; HYDROXY COMPOUNDS; Hyperlipoproteinemia Type II - genetics; ISOTOPES; LIGHT NUCLEI; LIPIDS; LIPOPROTEINS; Lipoproteins, LDL - metabolism; Medical sciences; MEMBRANE PROTEINS; Metabolic diseases; Molecular Sequence Data; Mutation; MUTATIONS; NUCLEI; NUCLEIC ACIDS; ODD-ODD NUCLEI; Oligonucleotides; ORGANIC COMPOUNDS; Pedigree; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; Polymerase chain reaction; Polymorphism, Restriction Fragment Length; PROTEINS; RADIOISOTOPES; RECEPTORS; Receptors, LDL - metabolism; RECOMBINANT DNA; STEROIDS; STEROLS; STRUCTURAL CHEMICAL ANALYSIS; Apolipoprotein B; Human; Allele; Hypercholesterolemia; Nucleotide sequence; Family study; Deficiency; Lipids; Metabolic diseases; Mutation; Haplotype; Aminoacid sequence
• DOI: 10.1073/pnas.86.2.587
• ISSN: 0027-8424

Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational ``hot spot,'' defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia.