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

Angela Pirillo, Katia Garlaschelli, Marcello Arca, Maurizio Averna, Stefano Bertolini, Sebastiano Calandra, Patrizia Tarugi, Alberico L. Catapano, Marcello Arca, Maurizio Averna, Stefano Bertolini, Sebastiano Calandra, Alberico L. Catapano, Patrizia Tarugi, Fabio Pellegatta, Francesco Angelico, Marcello Arca, Maurizio Averna, Andrea Bartuli, Giacomo BiasucciGianni 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, Andrea Giaccari, Francesco Giorgino, Ornella Guardamagna, Arcangelo Iannuzzi, Lorenzo Iughetti, Graziana Lupattelli, Giuseppe Mandraffino, Rossella Marcucci, Giuliana Mombelli, Sandro Muntoni, Riccardo Sarzani, Josè Pablo Werba, Liliana Grigore, Paola Sabrina Buonuomo, Maria Elena Capra, Marco Gentile, Maria Donata Di Taranto, Alberico L. Catapano, LIPIGEN Group

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalAtherosclerosis Supplements
Volume29
DOIs
Publication statusPublished - Oct 1 2017

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Keywords

  • APOB
  • Familial hypercholesterolemia
  • LDLR
  • Pathogenic variants
  • PCSK9

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Pirillo, A., Garlaschelli, K., Arca, M., Averna, M., Bertolini, S., Calandra, S., Tarugi, P., Catapano, A. L., Arca, M., Averna, M., Bertolini, S., Calandra, S., Catapano, A. L., Tarugi, P., Pellegatta, F., Angelico, F., Arca, M., Averna, M., Bartuli, A., ... LIPIGEN Group (2017). Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study. Atherosclerosis Supplements, 29, 17-24. https://doi.org/10.1016/j.atherosclerosissup.2017.07.002