148171 20250114175434.0 doi 10.1016/j.atherosclerosis.2019.11.025 sideral 115763 ART-2020-115763 eng Lamiquiz-Moneo, I. (orcid)0000-0002-9647-0108 Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia 2020 Background and aims: Autosomal dominant familial hypercholesterolemia (FH) is caused by mutations in LDLR, APOB and PCSK9. Two new putative loci causing FH have been identified recently, the p.(Leu167del) mutation in APOE and new mutations in the signal transducing adaptor family member STAP1. We aimed at investigating the role of STAP1 mutations in the etiology of FH. Methods: We sequenced LDLR, APOB, PCSK9, LDLRAP1, APOE, LIPA and STAP1 with the LipidInCode platform in 400 unrelated subjects from Spain with a clinical diagnosis of FH. All subjects carrying rare predicted pathogenic variants in STAP1 gene, described as pathogenic by at least three bioinformatic analysis and having an allelic frequency lower than 1% in general population, were selected for family study. Available relatives were recruited, including both hypercholesterolemic and non-hypercholesterolemic family members. Results: Sequencing analysis of STAP1 gene revealed seventeen rare variants, four of them being described as pathogenic by bioinformatic analysis. We studied the cosegregation with hypercholesterolemia of four rare predicted pathogenic variants, c.-60A > G, p.(Arg12His), p.(Glu97Asp), p.(Pro176Ser) in seven families. We did not observe any cosegregation between genotype and phenotype, even carriers of rare variants in STAP1 had lower LDL cholesterol levels than non-carriers. Conclusions: This study analyzes the family cosegregation of four rare predicted pathogenic variants of STAP1, p.(Arg12His), p.(Glu97Asp), p.(Pro176Ser) and c.-60A > G, in seven families, showing absence of cosegregation in all of them. These results would suggest that STAP1 gene is not involved in hypercholesterolemia of these families. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/DGA/B14-17R info:eu-repo/grantAgreement/ES/MINECO/PI18-01777 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.162 2020 PERIPHERAL VASCULAR DISEASE 14 / 65 = 0.215 2020 Q1 T1 CARDIAC & CARDIOVASCULAR SYSTEMS 43 / 141 = 0.305 2020 Q2 T1 1.554 2020 Cardiology and Cardiovascular Medicine 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Restrepo-Córdoba, M.A. Mateo-Gallego, R. Universidad de Zaragoza (orcid)0000-0001-6650-8294 Bea, A.M. del Pino Alberiche-Ruano, M. García-Pavía, P. Cenarro, A. Martín, C. Civeira, F. Universidad de Zaragoza (orcid)0000-0001-7043-0952 Sánchez-Hernández, R.M. 1006 255 Universidad de Zaragoza Dpto. Fisiatría y Enfermería Área Enfermería 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 292 (2020), 143-151 Atherosclerosis Atherosclerosis 0021-9150 6917171 http://zaguan.unizar.es/record/148171/files/texto_completo.pdf Postprint 1845852 http://zaguan.unizar.es/record/148171/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:148171 articulos driver 2025-01-14-15:48:46 ARTICLE