Phenotype of definite familial hypercholesterolemia with negative genetic study in Argentina.

Autor:	Corral P; Cátedra de Farmacología, Facultad de Medicina, Universidad FASTA. Buenos Aires, Argentina., Bañares V; Departamento de Genética Experimental, Centro Nacional de Genética Medica 'Dr. Eduardo Castilla', Administración Nacional de Laboratorios e Institutos de Salud 'Dr. Carlos Malbran'. Buenos Aires, Argentina., Sáenz B; Departamento de Investigación, Facultad de Medicina, Universidad FASTA. Buenos Aires, Argentina., Zago V; Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Universidad de Buenos Aires, Laboratorio de Lípidos y Aterosclerosis, INFIBIOCUBA. Buenos Aires, Argentina., Sarobe A; Cátedra de Farmacología, Facultad de Medicina, Universidad FASTA. Buenos Aires, Argentina., López G; Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Universidad de Buenos Aires, Laboratorio de Lípidos y Aterosclerosis, INFIBIOCUBA. Buenos Aires, Argentina., Berg G; Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Universidad de Buenos Aires, Laboratorio de Lípidos y Aterosclerosis, INFIBIOCUBA. Buenos Aires, Argentina., Schreier L; Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Universidad de Buenos Aires, Laboratorio de Lípidos y Aterosclerosis, INFIBIOCUBA. Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Archivos de cardiologia de Mexico [Arch Cardiol Mex] 2020; Vol. 90 (2), pp. 130-136.
DOI:	10.24875/ACME.M20000106
Abstrakt:	Objective: Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score > 8 points qualifies the patient as "definite" for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment. Methods: In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score > 8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c. Results: Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score > 8 did not show any genetic alteration. Conclusions: We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods. (Copyright: © 2020 Permanyer.)
Databáze:	MEDLINE
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