Xanthomatosis, Susceptibility To

Vergopoulos et al. (1997) studied a consanguineous Syrian kindred containing 6 individuals homozygous for a cys646-to-arg mutation in the LDLR gene (606945) resulting in familial hypercholesterolemia (143890). Half of the homozygotes had giant xanthomas, while half did not, even though their LDL-cholesterol concentrations were elevated to similar degrees. Heterozygous FH individuals in this family were also clearly distinguishable with respect to xanthoma size. Segregation analysis suggested the existence in this family of a second gene that determined the development of giant xanthomas when present in combination with the cys646-to-arg mutation.