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

Andrea Giaccari, Paola Sabrina Buonuomo, Vinsin Alice Sun, Angela Pirillo, Katia Garlaschelli, Marcello Arca, Maurizio Averna, Stefano Bertolini, Sebastiano Calandra, Patrizia Tarugi, Alberico Luigi Catapano, Marcello Arca, Maurizio Averna, Stefano Bertolini, Sebastiano Calandra, Fabio Pellegatta, Francesco Angelico, Marcello Arca, Maurizio Averna, Andrea BartuliGiacomo Biasucci, Gianni Biolo, Luca Bonanni, Katia Bonomo, Claudio Borghi, Antonio Carlo Bossi, Adriana Branchi, Francesca Carubbi, Francesco Cipollone, Nadia Citroni, Massimo Federici, Claudio Ferri, Anna Maria Fiorenza, Francesco Giorgino, Ornella Guardamagna, Arcangelo Iannuzzi, Lorenzo Iughetti, Graziana Lupattelli, Giuseppe Mandraffino, Rossella Marcucci, Giuliana Mombelli, Sandro Muntoni, Valerio Pecchioli, Cristina Pederiva, Antonio Pipolo, Livia Pisciotta, Arturo Pujia, Francesco Purrello, Elena Repetti, Paolo Rubba, Carlo Sabbà, Tiziana Sampietro, Riccardo Sarzani, Milena Paola Tagliabue, Chiara Trenti, Giovanni Battista Vigna, Josè Pablo Werba, Sabina Zambon, Maria Grazia Zenti, Anna Montali, Davide Noto, Stefano Bertolini, Sebastiano Calandra, Giuliana Fortunato, Liliana Grigore, Maria Del Ben, Marianna Maranghi, A. Baldassarre Cefalù, Maria Elena Capra, Pierandrea Vinci, Sergio D'Addato, Stella Galbiati, Fabio Nascimbeni, Marco Bucci, Walter Spagnoli, Iris Cardolini, Nazzareno Cervelli, Colombo Emanuela, 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, Bonora Enzo, Ilenia Minicocci, Rossella Spina, Camilla Orlando, Maria Donata Di Taranto, Manuela Casula, Lorenzo Chiodo, Katia Garlaschelli, Enzo Manzato, Elena Tragni

Risultato della ricerca: Contributo in rivistaArticolo in rivista

34 Citazioni (Scopus)

Abstract

Background 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). Methods 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). Results 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. Conclusions 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.
Lingua originaleEnglish
pagine (da-a)17-24
Numero di pagine8
RivistaAtherosclerosis Supplements
Volume29
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • APOB
  • Cardiology and Cardiovascular Medicine
  • Familial hypercholesterolemia
  • Internal Medicine
  • LDLR
  • PCSK9
  • Pathogenic variants

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