6533b82dfe1ef96bd1291512
RESEARCH PRODUCT
Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study
Angela PirilloKatia GarlaschelliMarcello ArcaMaurizio AvernaStefano BertoliniSebastiano CalandraPatrizia TarugiAlberico L. CatapanoMarcello ArcaMaurizio AvernaStefano BertoliniSebastiano CalandraAlberico Luigi CatapanoPatrizia TarugiFabio PellegattaFrancesco AngelicoMarcello ArcaMaurizio AvernaAndrea BartuliGiacomo BiasucciGianni BioloLuca BonanniKatia BonomoClaudio BorghiAntonio Carlo BossiAdriana BranchiFrancesca CarubbiFrancesco CipolloneNadia CitroniMassimo FedericiClaudio FerriAnna Maria FiorenzaAndrea GiaccariFrancesco GiorginoOrnella GuardamagnaArcangelo IannuzziLorenzo IughettiGraziana LupattelliGiuseppe MandraffinoRossella MarcucciGiuliana MombelliSandro MuntoniValerio PecchioliCristina PederivaAntonio PipoloLivia PisciottaArturo PujiaFrancesco PurrelloElena RepettiPaolo RubbaSabbã Carlo Tiziana SampietroRiccardo SarzaniMilena Paola TagliabueChiara TrentiGiovanni Battista VignaJosã Pablo WerbaSabina ZambonMaria Grazia ZentiAnna MontaliDavide NotoStefano BertoliniSebastiano CalandraGiuliana FortunatoLiliana GrigoreMaria Del BenMarianna MaranghiA. Baldassarre Cefalã¹Paola Sabrina BuonuomoMaria Elena CapraPierandrea VinciSergio D'addatoStella GalbiatiFabio NascimbeniMarco BucciWalter SpagnoliIris CardoliniNazzareno CervelliColombo EmanuelaVinsin A. SunLuigi LaviolaFrancesca BelloGiuseppe ChiarielloBarbara PredieriDonatella SiepiAntonino SaittaBetti GiustiChiara PavanelloMilena LussuLucia PratiGiuseppe BanderaliGiulia BalleariTiziana MontalciniRoberto ScicaliLuigi GentileMarco GentilePatrizia SuppressaFrancesco SbranaGuido CocciAndrea BensoEmanuele Alberto NegriOmar GhirardelloVigo LorenzoAlberto ZambonBonora EnzoIlenia MinicocciRossella SpinaCamilla OrlandoPatrizia TarugiMaria Donata Di TarantoAlberico Luigi CatapanoManuela CasulaLorenzo ChiodoKatia GarlaschelliEnzo ManzatoElena Tragnisubject
0301 basic medicineApolipoprotein ECandidate geneSettore MED/09 - Medicina InternaDatabases FactualApolipoprotein BDNA Mutational AnalysisFamilial hypercholesterolemia030204 cardiovascular system & hematologyCompound heterozygosityPCSK90302 clinical medicineRisk FactorsReceptorsGeneticsHomozygoteAutosomal dominant traitPathogenic variantsGeneral MedicinePrognosisAPOB; Familial hypercholesterolemia; LDLR; PCSK9; Pathogenic variantsCholesterolPhenotypeItalyAutosomal Recessive HypercholesterolemiaApolipoprotein B-100lipids (amino acids peptides and proteins)Proprotein Convertase 9APOBCardiology and Cardiovascular MedicinePreliminary DataGenetic MarkersFamilial hypercholesterolemiaLDLRPCSK9APOBPathogenic variantsHeterozygoteFamilial hypercholesterolemiaBiologyPathogenic variantLDLHyperlipoproteinemia Type II03 medical and health sciencesDatabasesmedicineInternal MedicineHumansAPOB; Familial hypercholesterolemia; LDLR; Pathogenic variants; PCSK9; Internal Medicine; Cardiology and Cardiovascular MedicineGenetic Predisposition to DiseaseFactualPCSK9Settore MED/13 - ENDOCRINOLOGIAAPOB; Familial hypercholesterolemia; LDLR; Pathogenic variants; PCSK9; Cardiology and Cardiovascular Medicine; Internal Medicinemedicine.diseaseAtherosclerosis030104 developmental biologyLDLRReceptors LDLMutationbiology.proteinAPOB; Familial hypercholesterolemia; LDLR; Pathogenic variants; PCSK9; Apolipoprotein B-100; Atherosclerosis; Cholesterol; DNA Mutational Analysis; Databases Factual; Genetic Markers; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Hyperlipoproteinemia Type II; Italy; Phenotype; Preliminary Data; Prognosis; Proprotein Convertase 9; Receptors LDL; Risk Factors; Mutation; Internal Medicine; Cardiology and Cardiovascular Medicinedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 |