PHENOTYPE OF DEFINITE FAMILIAL HYPERCHOLESTEROLEMIA WITH NEGATIVE GENETIC STUDY IN ARGENTINA

CORRAL, PABLO; BAÑARES, VIRGINIA; GELLER, ANDREW; POLISECKI, ELIANA; LOPEZ GRACIELA; BERG, GABRIELA ; SCHAEFER, ERNST; SCHREIER , LAURA

Maastricht

Congreso; 87 EAS Congress; 2019

European Atherosclerosis Society

Familial Hypercholesterolemia (FH) is a monogenic disease, associated with variants in the RLDL, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria, such as the Dutch Lipid Clinic Network (DLCN). A score of > 8 points qualifies the patient as "definitive" for the diagnosis of FH. In the framework of the FH Detection Program in Argentina - Da Vinci Study - 246 hypercholesterolemic patients were evaluated, 21 with a DLCN score > 8 (definitive diagnosis). These patients were studied with next-generation sequencing for the detection of genetic variants, with an extended panel of 23 genes, in addition to the analysis of large rearrangements and finally, a polygenic score of 10 SNP (single nucleotide polymorphism) related to high level of LDL-C. Of the 21 patients, 10 presented variants in the RLDL, 1 in APOB with APOE, 1 in LIPC plus high polygenic score, 2 patients with a deletion and a duplication in LDLR and the latter case with a variant in LIPA. It is highlighted that 6 of the 21 patients with a DLCN score > 8 did not show any genetic alteration. We can conclude that 28% of the patients with definitive clinical diagnosis of FH did not show genetic alteration. Possible explanations for this result would be the presence of mutations in new genes, the confusing effects of the environment on the genes or the gene-gene interaction, and finally the impossibility of detecting variants with the current available methodology.