[Study of low density lipoprotein (LDL) receptor mutations, using restriction endonucleases, in familial...

Familial hypercholesterolemia (FH) is an autosomal dominant metabolic disorder caused by different mutations in the low density lipoprotein receptor (LDLR) gene. We analyzed 13 families (23 patients) with FH and 36 subjects with normocholesterolemia by restriction fragment polymorphism (RFLP) using enzymes Xbal, BgIII and PvuII. At the 3' end of LDLR an extra 4.4 kb band has been found by Xbal digestion in one patient and it has been proved to be a "de novo" form of mutation. In the 5' end of LDLR gene a combined mutation has been identified in two FH families. The Xbal RFLP has yielded an extra band of 24.5 kb and an another extra band of 17.5 kb has been found by BgIII digestion. It has been suggested that the simultaneous occurrence of 3.3 kb extended deletion (intron 3) and 4.8 kb extended insertion (intron 1) is present. In our study the frequency of P2 allele (PvuII RFLP) in FH patients did not differ from normocholesterolemic controls.