Clinical familial hypercholesterolemia has been shown to result from mutations 
in 2 genes, the low density lipoprotein (LDL) receptor on chromosome 19 and 
apolipoprotein B on chromosome 2. However, we have recently described a Utah 
pedigree in which linkage to both genes was clearly excluded. A multipoint 
linkage analysis of 583 markers genotyped on 31 (18 affected) members of this 
pedigree was undertaken to localize a genetic region that may harbor a third 
gene that could result in clinical familial hypercholesterolemia. A multipoint 
log of the odds score of 6.8 was obtained for markers on 1p32. Haplotype 
carriers and affected status are completely concordant (18/18 persons). The 
phenotype is also expressed in young children (ages 4 and 9). Specific 
recombinant individuals in the pedigree restrict the region of linkage to an 
approximately 17 cM interval between polymorphic markers D1S2130 and D1S1596. 
This region appears to overlap the region found linked to severe 
hypercholesterolemia in French and Spanish families. The identification of the 
gene in this region may provide important pathophysiological insights into new 
mechanisms that may lead to highly elevated LDL cholesterol and other associated 
dyslipidemic phenotypes.