Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by high levels of circulating low-density lipoprotein (LDL) and premature coronary heart events. A quarter of the population of Southern Brazil is affected by hypercholesterolemia and the region has the highest mortality rates due to cardiovascular disease in the country. The aim of this study was to describe LDLR mutations in European descendants with FH living in Southern Brazil. Ten mL of venous blood were taken from 40 patients and used for DNA extraction and subsequent Polymerase Chain Reaction (PCR). The DNA fragments were sequenced and analyzed and the data obtained were compared to reference values from the University of California Santa Cruz (UCSC) Genome Browser. A total of 15 mutations were identified in 38 patients (95% of the total samples). These mutations were located in exons 11 (P518L) and 15 (D727G) in Italian, Portuguese and Spanish descendants and the *105T>G mutation, still undescribed, should be critically evaluated by means of mRNA alteration studies. The present study demonstrated for the first time the presence of the P518L mutation located in exon 11 of the LDLR gene in European descendants living in southern Brazil. This mutation has a high potential to be pathogenic since it is located in a domain responsible for LDLR release from the endoplasmic reticulum (ER).
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