Prevalence of Lithuanian mutation among St. Petersburg Jews with familial hypercholesterolemia.

We used polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis to detect LDL receptor gene defects in the St. Petersburg population. We have found a deltaG197 mutation in several patients of Jewish origin. The mutation named is shown to be responsible for one-third (7/23) of familial hypercholesterolemia (FH) cases in St. Petersburg Jews and absent in patients of Russian descent. The prevalence of a deltaG197 mutation in St. Petersburg Jews is consistent with its origin in Lithuania or Poland. The deltaG197 mutation can be easily detected in polyacrylamide minigels because of formation of specific heteroduplexes during PCR with DNA of heterozygous patients. Taken together with high prevalence of the mutation in St. Petersburg Jews, this observation provides an opportunity for DNA diagnostics of FH in this ethnic group.

Two novel low-density lipoprotein receptor gene mutations (E397X and 347delGCC) in St. Petersburg familial hypercholesterolemia.

Familial hypercholesterolemia (FH), a monogenic disease known to be caused by low-density lipoprotein receptor (LDLR) gene mutations, results in the development of premature atherosclerosis and coronary artery disease in affected individuals. The spectrum of LDLR gene mutations in Russia is poorly known. Using polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP) analysis, followed by DNA sequencing, we have screened selected exons of the LDLR gene in 80 unrelated St. Petersburg FH patients for the presence of mutations. Two new LDLR gene mutations, 347delGCC and E397X, were characterized among individuals with familial hypercholesterolemia in St. Petersburg. The carriers of both mutations possessed highly elevated blood serum cholesterol. Cosegregation of E397X mutation and LDLR gene RFLP haplotypes with hyperlipidemia was demonstrated by family study. Both mutations seem to be specific to Slavic patients.