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Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

2017; Elsevier BV; Volume: 29; Linguagem: Inglês

10.1016/j.atherosclerosissup.2017.07.002

1878-5050

Angela Pirillo, K. Garlaschelli, Marcello Arca, Maurizio Averna, S Bertolini, S. Calandra, Patrizia Tarugi, Alberico L. Catapano, Marcello Arca, Maurizio Averna, S Bertolini, S. Calandra, Alberico L. Catapano, Patrizia Tarugi, Fabio Pellegatta, Francesco Angelico, Marcello Arca, Maurizio Averna, Andrea Bartuli, Giacomo Biasucci, Gianni Biolo, Luca Bonanni, Katia Bonomo, Claudio Borghi, Antonio Bossi, Adriana Branchi, Francesca Carubbi, Francesco Cipollone, Nadia Citroni, Massimo Federici, Claudio Ferri, A.M. Fiorenza, Andrea Giaccari, Francesco Giorgino, Ornella Guardamagna, Marcello Arca, Lorenzo Iughetti, Graziana Lupattelli, Giuseppe Mandraffino, Rossella Marcucci, Giuliana Mombelli, Sandro Muntoni, Valerio Pecchioli, Cristina Pederiva, A. E. Pípolo, Livia Pisciotta, Arturo Pujia, Francesco Purrello, Elena Repetti, Paolo Rubba, Carlo Sabbà, Tiziana Sampietro, Riccardo Sarzani, Milena Tagliabue, Chiara Trenti, Giovanni Battista Vigna, José Pablo Werba, Sabina Zambon, Maria Grazia Zenti, Anna Montali, Davide Noto, S Bertolini, S. Calandra, Giuliana Fortunato, Liliana Grigore, Maria Del Ben, Marianna Maranghi, Angelo Baldassarre Cefalù, Paola Sabrina Buonuomo, Maria Elena Capra, Pierandrea Vinci, Sergio D’Addato, Stella Galbiati, Fabio Nascimbeni, Marco Bucci, Walter Spagnoli, Iris Cardolini, Nazzareno Cervelli, Emanuela Colombo, Vinsin A. Sun, Luigi Laviola, Francesca Bello, Giuseppe Chiariello, Barbara Predieri, Donatella Siepi, Antonino Saitta, Betti Giusti, Chiara Pavanello, Milena Lussu, Lucia Prati, Giuseppe Banderali, Giulia Balleari, Tiziana Montalcini, Roberto Scicali, Luigi Gentile, Marco Gentile, Patrizia Suppressa, Francesco Sbrana, Guido Cocci, Andrea Benso, Emanuele Alberto Negri, Omar Ghirardello, Vigo Lorenzo, Alberto Zambon, Enzo Bonora, Ilenia Minicocci, Rossella Spina, Camilla Orlando, Patrizia Tarugi, Maria Donata Di Taranto, Alberico L. Catapano, Manuela Casula, Lorenzo Chiodo, K. Garlaschelli, Enzo Manzato, Elena Tragni,

Lipoproteins and Cardiovascular Health

Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress.