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Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Apolipoprotein E
Candidate gene
Settore MED/09 - Medicina Interna
Databases, Factual
Apolipoprotein B
DNA Mutational Analysis
Familial hypercholesterolemia
030204 cardiovascular system & hematology
Compound heterozygosity
PCSK9
0302 clinical medicine
Risk Factors
Receptors
Genetics
Homozygote
Autosomal dominant trait
Pathogenic variants
General Medicine
Prognosis
APOB
LDLR
Cholesterol
Phenotype
Italy
Autosomal Recessive Hypercholesterolemia
Apolipoprotein B-100
lipids (amino acids, peptides, and proteins)
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
Preliminary Data
Genetic Markers
Familial hypercholesterolemiaLDLRPCSK9APOBPathogenic variants
Heterozygote
Biology
Pathogenic variant
LDL
Hyperlipoproteinemia Type II
03 medical and health sciences
Databases
medicine
Internal Medicine
Humans
Genetic Predisposition to Disease
Factual
Settore MED/13 - ENDOCRINOLOGIA
medicine.disease
Atherosclerosis
030104 developmental biology
Receptors, LDL
Mutation
biology.protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....a36d090710c5eadfd34a3c093d4e8620