HETEROGENEITY IN THE PATTERN OF FAMILIAL HYPERCHOLESTEROLEMIA MUTATIONS IN A POPULATION OF THE SOUTH-EAST OF BUENOS AIRES

BAÑARES, VIRGINIA; CORRAL, PABLO; POLISECKI, ELIANA; LOPEZ G; CACCIAGIU, LEONARDO; BERG, GABRIELA; SCHREIER , LAURA

buenos aires

Congreso; Reunion Conjunta de sociedades de Biociencias; 2017

Sociedades de biociencias

Familial Hypercholesterolemia (FH) is a common genetic cause ofpremature coronary heart disease (CHD), widely underdiagnosed.Genetic testing allows the early identification and then the decisionof treatment contributing to prevent the CHD. So far, we did not havegenetic data from the same area of the country. Here we describe themutation pattern across the main FH genes, LDLR, APOB, PCSK9,plus LDLRAP1 gene of the recessive form, in patients assisted ata Medical Center depending on the Health Direction from GeneralPueyrredon-BA. From the ?First Prevalence Study of FamilialHypercholesterolemia in Argentina? 247 blood samples of patients≥18 years with c-LDL ≥190mg/dl were selected. According to theDUTCH Clinic Lipid Network criteria, 72 selected patients have clinicdiagnosis of probable FH (score 6-8) or definitive (score>8). DNAwas obtained and the four genes were sequence in a MiSeq, Illumina.The variants were annotated using reference sequences Hg19and classified according to ACMG-2015, in silico tests were appliedfor novels and VUS variants. Mutations, related to FH, were find in20 subjects (30%): 17 in the LDLR (85%) and 3 in APOB (15%).All variants were in heterozygosis; two, on the LDLR, were seen inmore than one patient: c.1027G>A (p.G343S) in 4 and c.1567G>A(p.V523M) in 2 cases; 2 were novels; the most frequent APOB variantin Caucasian, c.10580G>A (p.R3527Q), was observed once andthe Lebanese mutation in LDLR, that had been previously foundmore frequent in a general study, was not observed. Conclusion: FHmutations show an important heterogeneity in our population. Knowingthe spectrum of mutations will allow us to develop strategies thatare adequate to approach their study in our population.