engleski

A novel missense mutation C127R (FH ZAGREB) in the LDL-receptor gene causing familial hypercholesterolemia

We have employed analysis of single-strand conformation polymorphisms to identify mutations in the exon 4 of the low density lipoprotein receptor gene causing familial hypercholesterolemia. Three familial hypercholesterolemia heterozygotes had abnormal single-strand conformation polymorphism patterns. DNA sequencing revealed that the abnormal pattern of exon 4A was due to heterozygosity (T/C) at nucleotide 442. Nucleotide 442 is the first base of codon 127, and the TŽC mutation (C127R) changes this codon from CysTGT to ArgCGT. The abnormal patterns of exon 4B were due to heterozygosity (A/G) at nucleotide 662. Nucleotide 662 is the second base of codon 200, and the AŽG mutation (D200G) changes this codon from AspGAC to GlyGGC. Mutation D200G was previously described as FH-Padova, but mutation C127R has not been reported previously. The novel mutation was confirmed by restriction endonuclease analysis with Dsa I. Based upon screening of 420 familial hypercholesterolemia heterozygotes both C127R and D200G account for about 0.7% of the mutations causing familial hypercholesterolemia in Croatia.

LDL receptor; mutation; RFLP

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