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 d evelopment of premature atherosclerosis and coronary artery disease in affe cted individuals. The spectrum of LDLR gene mutations in Russia is poorly k nown. Using polymerase chain reaction (PCR)-single-strand conformational po lymorphism (SSCP) analysis, followed by DNA sequencing, we have screened se lected exons of the LDLR gene in 80 unrelated St. Petersburg FH patients fo r the presence of mutations. Two new LDLR gene mutations, 347delGCC and E39 7X, were characterized among individuals with familial hypercholesterolemia in St. Petersburg. The carriers of both mutations possessed highly elevate d blood serum cholesterol Cosegregation of E397X mutation and LDLR gene RFL P haplotypes with hyperlipidemia was demonstrated by family study. Both mut ations seem to be specific to Slavic patients. (C) 1998 Academic Press.