Familial hypobetalipoproteinemia: Analysis by next generation sequencing and identification of a novel frameshift mutation in the apoB gene

Mutation in candidate genes account for a small minority of hypobetalipoproteinemias and NGS analysis support polygenicity in mutation-negative patients

Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia identified in the lipigen centre of Palermo

Clinical and genetic features of 2 patients with severe hypertriglyceridemia due to a mutation in GPIHBP1 gene

Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia in sicily

Aim: Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant disorder characterized by high serum low density lipoproteincholesterol (LDL-C) levels. The clinical manifestations of ADH might vary among affected subjects and the phenotype correlates with the severity of mutation and the specific gene involved. The aim of this study was to evaluate the clinical expression and clinical outcomes in a cohort of ADH subjects. Methods: 300 ADH probands with a DUTCH score > 6 were enrolled in this study and the analysis was extended to the family members of these index cases. Anthropometric measures, clinical and biochemical parameters, life style (smoker and/or alcohol habits) and…

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing

Background Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. Objective The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG. Methods We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL–10 mmol/L): 4 positive controls in whom pathogenic mutations had pre…

Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred.

Background Autosomal recessive hypercholesterolemia (ARH) is a rare inherited lipid disorder. In Sardinia, differently from other world regions, the mutated allele frequency is high. It is caused by mutations in the low-density lipoprotein receptor adaptor protein 1 gene. Fourteen different mutations have been reported so far; in Sardinia, 2 alleles (ARH1 and ARH2) explain most of the cases. Four ARH patients, all carriers of the ARH1 mutation, have been identified in mainland Italy and 2 in Sicily. Objective The objectives of the study were to improve the molecular diagnosis of familial hypercholesterolemia (FH) and to estimate the frequency of the ARH1 allele in 2 free-living Sicilian pop…

Identification Of P.Leu167Del Apoe Gene Mutation By Next Generation Sequencing In A Large Hypercholesterolemic Family

MOLECULAR CHARACTERIZATION OF PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE WITH "EXTREME LDL-C PHENOTYPES"

PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study.

Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradatio…

Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.

Objective— Cyclic AMP responsive element–binding protein 3–like 3 ( CREB3L3 ) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. Approach and Results— The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation …

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing

A NEXT GENERATION SEQUENCING APPROACH FOR MOLECULAR DIAGNOSIS OF MONOGENIC DYSLIPIDEMIAS

Prevalence Of Statin Intolerance In A Cohort Of Outpatients In A Lipid Clinic

rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography

Abstract Background and aims Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients. Methods and results The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected,…

Genetic epidemiology of ARH in Sicily