Identification of a 76-year-old patient with compound heterozygous familial hypercholesterolemia by haplotype analysis of the LDL receptor gene.

In a large family with clinical characteristics of heterozygous familial hypercholesterolemia (FH) seven restriction fragment length polymorphisms (RFLP) were used to determine low-density-lipoprotein receptor (LDLR) gene haplotypes. Following the inheritance of the LDL receptor genes characterized by their seven RFLP haplotypes, two different alleles were found to cosegregate with elevated cholesterol levels within this family. In a 76-year-old man both alleles identified as defective were present, thus classifying this individual as heterozygous compound for FH. In five heterozygous family members one allele was associated with 38% higher cholesterol levels when compared to the other mutant allele in two heterozygous family members. Cosegregation of hypercholesterolemia with the apolipoprotein B (apoB) gene and apolipoprotein E (apoE) gene was excluded by genotyping all individuals for the apoB XbaI RFLP and apoE polymorphisms. These findings are consistent with variable phenotypic expression of the mutant LDLR gene alleles.