0000000000463732
AUTHOR
Angelo Baldassare Cefalu'
Identification of a novel ANGPTL3 mutation splicing associeted to severe hypobetalipoproteinemia
Introduction. Primary hypobetalipoproteinemia (pHBL) is a monogenic heterogeneous condition inherited as a dominant or recessive trait characterized by total cholesterol (TC) and/or LDL cholesterol (LDL-C) and/or apolipoprotein B (APOB) levels below the 5th percentile of the reference population. Heterozygous APOB gene mutations are responsible for the majority of the dominant pHBL causing the familial hypobetalipoproteinemia (FHBL). Loss-of-function mutations in the PCSK9 gene also cause FHBL. Familial combined hypolipidemia is a recently discovered dyslipidemic phenotype characterized by low levels of TC, triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol (HDL-C). The gen…
METALLOTHIONEIN 2A: A POSSIBLE CANDIDATE ABLE TO INTERACT WITH LDL-R CYTOPLASMIC TAIL
COMPOUND HETEROZYGOUS FH AND FDB: IDENTIFICATION OF A SICILIAN FAMILY HARBOURING THE FDB3531 MUTATION AND THE Y398X MUTATION OF THE LDL RECEPTOR GENE.
PREVALENCE OF ANGPTL3 AND APOB GENE MUTATIONS IN SUBJECTS WITH COMBINED HYPOLIPIDEMIA
Introduction. Mutations of the ANGPTL3 gene have been found responsible for a novel form of primary hypobetalipoproteinemia (pHBL), the combined hypolipidemia, characterized by low total cholesterol (TC) and low HDL-cholesterol (HDL-C) levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in two large cohorts of 913 American and Italian subjects with primary hypobetalipoproteinemia (TC <5th percentile). Materials and Methods. The cut-offs adopted to define the combined hypolipidemia phenotype were chosen taking into account the TC and HDL-C levels reported in the ANGPTL3 kindred described to date and are as follows: TC leve…
A NOVEL COMPOUND HETEROZYGOUS MUTATION OF THE LIPOPROTEIN LIPASE GENE IN A NEWBORN WITH CHYLOMICRONEMIA
Saturated and unsaturated free fatty acids (FFA) modulate differently HDL uptake in hepatoma HEPG2 cells
No association of Cystatin C Polymorphism I in italian subjects with Alzheimer's disease
NEXT GENERATION SEQUENCIN: A NEW METHODOLOGICAL APPROACH FOR THE MOLECULAR DIAGNOSIS OF GENETIC DYSLIPIDEMIAS
Terapia biologica con infliximab (anti-TNF) nella malattia di Crohn: analisi delle complicanze.
Anti-tumor necrosis factor (anti-TNF) therapy is an important therapeutic addition in the treatment of active Crohn's disease. Although controlled trials have confirmed the efficacy of anti-TNF (infliximab) treatment, serious toxicities related to the therapies have emerged. The purpose of this article was to review the safety profile of infliximab, and in particular analyse the infectious complications, the autoimmune disorders and the theoretical risk of cancer and lymphoma
Clinical, molecular and functional characterization of two novel mutations associated to compound heterozygous FHBL
Introduction. Primary hypobetalipoproteinemia (pHBL) is a monogenic heterogeneous condition characterized by total cholesterol (TC) and/or LDL cholesterol (LDL-C) levels below the 5th percentile of the reference population. Heterozygous APOB gene mutations are responsible for the majority of the dominant pHBL causing the familial hypobetalipoproteinemia (FHBL). The clinical phenotype of heterozygous FHBL is usually mild. The homozygous or compound heterozygous APOB mutations are in some cases responsible for a more severe biochemical and clinical phenotype, similar to the abetalipoproteinemia (ABL) due to homozygous mutations in the MTP gene, characterized by intestinal malabsorption, pigme…
LA LIPIDOMICA DELLA NON ALCOHOLIC FATTY LIVER DISEASE: ANALISI DELLA CINETICA DELL’ACIDO PALMITICO MEDIANTE L’USO DI UN ISOTOPO STABILE IN UN MODELLO IN VITRO
Variations in plasma lipids and in the LDL peak particle size after acute myocardial infarction
A novel mutation in the Lipase Maturaction Factor 1 (LMF-1)gene responsible for severe hypertriglyceridemia
A metallothionein family member interacts with the intracellular domain of the low density lipoprotein (LDL) receptor
Chilomicronemia transitoria causa di diabete di tipo I in assenza di markers umorali di autoimmunità in una bambina di nove anni
A NOVEL NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS
Il polimorfismo genico CD14 C(-260)>T non e’ un fattore di rischio per infarto miocardico acuto
Treatment of primary hypercholesterolemia: comparison of the effectiveness of different statins
VARIABLE PHENOTYPIC ESPRESSION IN A LIPID ABSORPTION DISORDER DUE TO A MOLECULAR DEFECT IN THE SARA2 GENE
FAMILIAL HYPOBETALIPOPROTEINEMIA DUE TO APOLIPOPROTEIN B GENE MUTATIONS CAUSES INTESTINAL FAT ACCUMULATION AND LIPID MALABSORPTION.
Prevalenza di fattori di rischio e variazione temporale dei parametri lipidici in una serie consecutiva di 350 infarti acuti del miocardio registrati in una unita’ intensiva di Palermo.
CLINICAL AND MOLECULAR CHARACTERIZATION OF HYPERCHOLESTEROLEMIC SICILIAN FAMILIES AND DESCRIPTION OF 3 NOVEL MUTATIONS IN THE LDLR GENE
Prothrombotic gene variants in AMI young women
INTERACTION OF THE INTRACELLULAR DOMAIN OF THE LOW DENSITY LIPOPROTEIN (LDL) RECPTOR WITH METALLOTHIONEIN2 (MT2).
IL GENE PCSK9: UN NUOVO GENE IMPLICATO NEL CONTROLLO DELLA COLESTEROLEMIA
The distribution of cholesterol plasma is regulated by complex interactions between genes and environmental factors. Mutations of PCSK9 gene seem to modulate the levels of LDL-C. Mutations of PCSK9 gene with gain of function are associated to hypercholesterolemia and mutations with loss of function determine hypocholesterolemia.
Lack of association of low density lipoprotein receptor-related protein gene exon 3 polymorphism in italian subjects with Alzheimer's disease
SEVERE MALABSORPTION AND DECREASED TRIGLYCERIDE RICH LIPOPROTEINS PRODUCTION IN A PROBAND CARRYING A MUTATION ENCODING FOR A TRUNCATED APOLIPOPROTEIN B100 VARIANT (APO B 34.8).
TERAPIA CON STATINE IN PAZIENTI SICILIANI AFFETTI DA IPERLIPIDEMIA FAMILIARE COMBINATA
Familial combined hyperlipidemia (FCHL) is the most frequent genetic hyperlipidemia. FHCL is associated with high prevalence of cardiovascular disease. In this study we selected 208 patients affected by FHCL and evaluated the efficacy of the lipid-lowering statin therapy using different statins available in the market. The results show that the percent of patients reaching the therapeutic goal ranges from 19.7 % (LDL-C <100 mg/dL) to 50.9% (LDL-C <130 mg/dL) and from 16.9 % (non HDL-C <130 mg/dL) to 46.6 % (non HDL-C <160 mg/dL) according to the different ATPIII-NCEP-guidelines cut offs. In conclusion the statin monotherapy is only partly effective in the management of FCHL therapy
Low-density-lipoprotein peak particle size in a Mediterranean population.
Background: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design: We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. Results: The prevalence of LDL phen…
I LIVELLI DI CISTATINA C SONO RIDOTTI NELL’INFARTO MIOCARDIO ACUTO. EFFETTO DEL POLIMORFISMO G73A SUI LIVELLI PLASMATICI.
HYPOBETALIPOPROTEINEMIA AND FATTY LIVER: WHO IS THE CULPRIT
Changes in levels of triglyceride-rich lipoprotein subfractions during dialysis in uremic patients
FISIOPATOLOGIA DELLA SINTESI DELLE LIPOPROTEINE INTESTINALI
La sintesi di lipoproteine di origine intestinale è un processo sequenziale, necessario per l’assorbimento dei lipidi e delle vitamine liposolubili di origine alimentare. L’assemblaggio dei chilomicroni inizia nel reticolo endoplasmico con la formazione di particelle ricche di fosfolipidi che sono poi trasportate al Golgi per essere secrete. Diverse classi di trasportatori giocano un ruolo sia nell’assorbimento selettivo che nel trasporto di lipidi attraverso i villi intestinali. Una volta secrete nel circolo linfatico, le lipoproteine ricche di trigliceridi (LRT) sono sottoposte all’azione della Lipasi Lipoproteica (LPL), che catalizza l’idrolisi dei triacilgliceroli delle lipoproteine a d…
Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study
Backgroundand aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.Results: This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0–65.5) y…
IDENTIFICATION OF A HETEROZYGOUS COMPOUND INDIVIDUAL WITH AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIA HARBOURING A MUTATION IN THE LDL-R GENE AND IN THE PCSK9 GENE
UNA NUOVA MUTAZIONE DELL’INTRONE 16 (G>A a 2390 -1) DEL RECETTORE DELLE LDL RESPONSABILE DI IPERCOLESTEROLEMIA FAMILIARE. EFFETTI SULLA ESPRESSIONE DELL’mRNA DEL RECETTORE DELLE LDL
CD14 C(-260)>T gene polymorphism is not a risk factor for myocardial infarction
A NOVEL APOB MUTATION IDENTIFIED BY EXOME SEQUENCING COSEGREGATES WITH STEATOSIS, LIVER CANCER AND HYPOCHOLESTEROLEMIA
Objective. In familial hypobetalipoproteinemia (FHBL), fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein (LDL) cholesterol, fatty liver and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results. The proband was a 25 year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis and four more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutat…
Transient chylomicronemic syndrome: description of three cases
FAMILIAL LIGAND-DEFECTIVE APOLIPOPROTEIN B: IDENTIFICATION OF A FAMILY HARBOURING THE ARG3531CYS (FDB3531) OF THE APOB GENE
Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.
Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even…
CEREBROTENDINOUS XANTHOMATOSIS: A SICILIAN FAMILY HARBOURING THE R362C MUTATION IN THE STEROL 27-HYDROXYLASE GENE
Descrizione di una famiglia siciliana con iper-alfa-lipoproteinemia con deficit di CETP
Accumulation of ApoE-containing triglyceride-rich lipoproteins in normolipidemic men with premature coronary artery disease
Studio epidemiologico “Ustica”: bassa prevalenza delle LDL aterogene in una popolazione mediterranea
ApoE polymorphism in a small Mediterranean island: Relationships with plasma lipids, lipoproteins and LDL particle size
Polymorphisms of apoE gene are able to modulate lipoprotein metabolism at different steps and to influence LDL-cholesterol (LDL-C) levels and also other lipoproteins features. Population studies documented large differences in the frequency of apoE alleles which could be even related to the prevalence of cardiovascular disease. In this study we evaluated the apoE genotypes and allele frequency in 576 subjects living in a small island in the Tyrrhenian Sea and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein profile, including LDL particle size. We found a cumulative frequency of 0.073, 0.866 and 0.061 for ε2, ε3 and ε4 alleles respectively. Moreover ε3 subjects…
ΒETA ARRESTIN-2: A NEW “ACTOR” IN THE LDL-R ENDOCYTOSIS?
Metabolomic analysis of plasma from Alzheimer disease patients
Alzheimer Disease is a degenerative disease characterized by progressive impairment of cognitive function. The main feature of AD the generation of an abnormal peptide, beta amyloid 42 (Ab42) from Amyloid Precursor Protein (APP). Ab42 is the main constituent of neurotangles and amyloid plaques, microscopic lesions found in AD patients brain. Ab42 triggers an inflammatory response that is responsible for most of the observed tissue damage. The diagnosis of AD is a complex task, mostly based on imaging techniques and clinical evaluation of the patient’s neurological and cognitive functions. The search for plasma biomarkers able to detect early mild cognitive impairment is one of the recent at…
Description of a sicilian family with hyper-alpha-lipoproteinemia with deficit of CETP activity
DIFFERENCE IN THE PREVALENCE OF METABOLIC SYNDROME AND CARDIOVASCULAR RISK FACTORS AFTER 14 YEARS IN THE POPULATION OF VENTIMIGLIA DI SICILIA
THE METABOLIC SYNDROME IS A PREDICTOR OF CARDIOVASCULAR EVENTS IN A SICILIAN POPULATION. RESULT OF A 15 YEARS FOLLOW UP
RUOLO DEL POLIMORFISMO ILE148MET DEL GENE PNPLA3 NELLA STEATOSI ASSOCIATA ALLA IPOBETALIPOPROTEINEMIA FAMILIARE
PREVALENCE OF PCSK9 VARIANTS IN A COHORT OF SUBJECTS WITH HYPOCHOLESTEROLEMIA
IPERCOLESTEROLEMIA AUTOSOMICA DOMINANTE IN SICILIA
Le variazioni dei valori dell’assetto lipidico durante la risposta di fase acuta post-infarto miocardico acuto sono accompagnate da modifiche nel size delle LDL
ASSOCIATION OF THE PARAOXONASE-1 Q192R POLYMORPHISM WITH CORONARY ARTERY DISEASE IN AMI PATIENTS, NON AMI CAD AND HEALTHY CONTROLS.
ENHANCED LIPID PEROXIDATION AND PLATELET ACTIVATION AS POTENTIAL CONTRIBUTORS TO INCREASED CARDIOVASCULAR RISK IN THE “LOW-HDL” PHENOTYPE.
THE METABOLIC SYNDROME PREDICTS CARDIOVASCULAR EVENTS IN SUBJECTS WITH NORMAL GLUCOSE TOLERANCE. A 15 YEARS FOLLOW-UP IN A MEDITERRANEAN POPULATION
A novel nonsense mutation in the cept gene in italian Hyperalphalipoproteinemic subjects
C-reactive protein but not soluble CD40 ligand and homocysteine is associated to common atherosclerotic risk factors in a cohort of coronary artery disease patients.
Abstract Objectives One third to one half of the variation in vascular disease occurrence remains unexplained by traditional risk factors. Since atherosclerosis may, in part, be an inflammatory disease, circulating factors related to inflammation may be predictors of cardiovascular disease. The aim of this study was to evaluate the association between common atherosclerotic risk factors and markers of inflammation. Design and methods Serum levels of soluble CD40 (sCD40L), high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) were measured in 251 patients selected from a series of 438 subjects affected by previous myocardial infarction, angina or other cardiovascular diseases. Re…
LDL size, density and receptor affinity variation during an oral load in mild hyper-triglyceridemic and normal subjects
Genetic heterogeneity of familial hypercholesterolemia in Sicily
VASCULOPROTECTIVE FUNCTION OF HDL FROM CETP-DEFICIENT SUBJECTS
Objective. Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of primary hyperalphalipoproteinemia and represents a unique tool to evaluate how structural HDL alterations impact on HDL atheroprotective activity. Aim of the present study was to assess the vasculoprotective activity of HDL isolated from carriers of genetic CETP deficiency. Subjects and Methods. HDL and HDL subfractions were isolated from carriers of the R37X, Q165X and IVS7+1 CETP mutations. HDL and HDL subfractions from carriers were tested for their protein/lipid …
Il polimorfismo genico del CD14 C(-260)>T non e’ un fattore di rischio per infarto miocardico acuto
NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS.
MUTATIONS IN THE CETP GENE IN ITALIAN SUBJECTS WITH HYPERALPHALIPOPROTEINEMIA
Levels of b-sitosterol in a sicilian sample of hyper-cholesterolemic patients
THE METABOLIC SYNDROME PREDICTS CARDIOVASCULAR EVENTS IN SUBJECTS WITH NORMAL FASTING GLUCOSE. A FIFTEEN YEARS FOLLOW-UP IN A MEDITERRANEAN POPULATION
MISSENSE MUTATION ALA34VAL IN EXON 2 OF THE LIPOPROTEIN LIPASE GENE IN A YOUNG MAN WITH CHYLOMICRONEMIA.
GLI ACIDI GRASSI SATURI ED INSATURI MODULANO L’UPTAKE DELLE LIPOPROTEINE HDL IN UN MODELLO DI CELLULE EPATICHE IN COLTURA.
DETECTION OF NEW GENES RESPONSIBLE OF FAMILIAL RECESSIVE HYPERCHOLESTEROLEMIA: PRELIMINARY DATA FROM AN EXOME SEQUENCING APPROACH
Low prevalence of the atherogenic small, dense LDL in a mediterranean population. Nutrition, Metabolism and Cardiovascular Diseases
MUTAZIONI DEL GENE DELL’APOB RESPONSABILI DI IPOBETALIPOPROTEINEMIA FAMILIARE IN SICILIA
Effects of PCSK9 inhibitors on HDL cholesterol efflux and serum cholesterol loading capacity in familial hypercholesterolemia subjects: a multi-lipid-center real-world evaluation.
Proprotein convertase subtilisin/kexin type 9 (PCSK9), beyond regulating LDL cholesterol (LDL-c) plasma levels, exerts several pleiotropic effects by modulating lipid metabolism in extrahepatic cells such as macrophages. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, including the HDL capacity to promote cell cholesterol efflux (CEC) and the serum capacity to promote cell cholesterol loading (CLC). The aim of this observational study was to investigate the effect of PCSK9 inhibitors (PCSK9-i) treatment on HDL-CEC and serum CLC in patients with familial hypercholesterolemia (FH). 31 genetically confirmed FH patients were recruited. Blood was collected and serum is…
A metallothionein family member interacts with the intracellular domain of the low density lipoprotein (ldl) receptor.
FUNCTIONAL EFFECT OF NOVEL AMINO ACID VARIANTS OF APOLIPOPROTEIN B IN FAMILIAL HYPOBETALIPOPROTEINEMIA
Introduction. Familial Hypobetalipoproteinemia (FHBL) is a codominant disorder characterized by reduced plasma levels of LDL-C and apolipoprotein (apo) B. In 50% of cases FHBL is due to mutations in APOB gene resulting in truncated apoBs of various size. Some mutations in APOB gene resulting in non-conservative amino acid substitutions were reported to cause FHBL. In vitro, these mutations induce the retention of the mutant apoB in the endoplasmic reticulum (ER) and impair the secretion of apoB-containing lipoproteins. In two FHBL subjects we identified two novel amino acid variants (Thr26_27delinsAsn and Tyr102Cys) located in the N-terminal 1000 amino acids of mature apoB. Methods. To inve…
Cystatin C levels are decreased in acute myocardial infarction: Effect of cystatin C G73A gene polymorphism on plasma levels
Background: Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. Methods: In this study, plasma levels of cystatin C have been investigated in patients with acute myocardial infarction (AMI), unstable angina and controls. The effect on plasma levels of the G73A polymorphism of the CST3 gene has been also evaluated. Results: Patients with acute myocardial infarction showed significantly lower levels of cystatin C compared to unstable angina and controls, but levels were nearly normal in a week after …
HETEROGENITY OF AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIA IN SICILY
Bassa prevalenza delle LDL aterogene piccole e dense in una popolazione mediterranea
Le LDL generate in fase post-prandiale dopo carico grasso presentano maggiore densita’, minore size e maggiore affinita’ per il recettore
HYPOALPHALIPOPROTEINEMIA ASSOCIATED TO CORNEAL OPACITIES IN ABSENCE OF LCAT DEFICIENCY.
HYPERTENSION AND DIABETES MELLITUS PREDICT CARDIOVASCULAR EVENTS IN ELDERLY WITHOUT CARDIOVASCULARDISEASE. RESULTS OF FIFTEEN YEARS FOLLOW-UP IN A MEDITERRANEAN POPULATION.
Accumulo di VLDL/IDL contenenti ApoE in maschi normolipemici con cardiopatia ischemica precoce
Simvastatin reduces the levels of ApoE-containing triglyceride-rich lipoproteins in men with premature coronary artery disease
SHORT APOB TRUNCATIONS SHOW IMPAIRE CHYLOMICRON EXPORT AND ENTEROCYTE TRIGLYCERIDE ACCUMULATION. IN VIVO AND IN VITRO EVIDENCE ON A APOB 28.25 STABLE-TRANSFECTED ENTEROCYTE CELL LINE
Variazioni delle sottofrazioni delle lipoproteine ricche in trigliceridi durante la dialisi in soggetti uremici
CD14 C(-260)>T gene polymorphism is not a risk factor for myocardial infarction
MUSCLE DAMAGE AND PAIN IN HYPERCHOLESTEROLEMIC OUT-PATIENTS POPULATION ON STATIN TREATMENT.
ASSOCIAZIONE DEL POLIMORFISMO Q192R DEL GENE DELLA PARAOXONASI I (PON1) CON LA MALATTIA CORONARICA IN UN CAMPIONE DI PZ CON INFARTO MIOCARDICO, MALATTIA CORONARICA NON INFARTUALE E SOGGETTI NORMALI.
INTERLEUKIN 6 PLASMA LEVELS PREDICT WITH HIGH SENSITIVITY AND SPECIFICITY CORONARY STENOSIS DETECTED BY CORONARY ANGIOGRAPHY
FUNCTIONAL CHARACTERIZATION OF NOVEL AMINO ACID VARIANTS IN APOB IN FAMILIAL HYPOBETALIPOPROTEINEMIA
Introduction. Familial Hypobetalipoproteinemia (FHBL) is a codominant disorder characterized by reduced levels of LDL and apolipoprotein B (apoB) in plasma. In approximately 50% of FHBL cases is due to mutations in APOB gene resulting in truncated apoBs of various size. Only a few missense mutations have been reported so far as the cause of FHBL. In vitro studies have shown that these mutations induce retention of the mutant apoB in the endoplasmic reticulum and impair the secretion of apoB-containing lipoproteins. We identi ed two novel amino acid variants (Thr26-27del and Tyr102Cys) located in the N-terminal 1000 amino acids of mature apoB in two hypocholesterolemic blood donors. Methods.…