159 results match your criteria Low LDL Cholesterol Hypobetalipoproteinemia


A Healthy Family of Familial Hypobetalipoproteinemia Caused by a Protein-truncating Variant in the PCSK9 Gene.

Intern Med 2020 15;59(6):783-787. Epub 2020 Mar 15.

Department of Cardiology, Kanazawa University Graduate School of Medicine, Japan.

We present the first case of a Japanese patient with familial hypobetalipoproteinemia (FHBL) caused by a protein-truncating variant in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. A 34-year-old woman was referred to our hospital due to her low low-density lipoprotein (LDL)-cholesterolemia (34 mg/dL). She did not have any secondary causes of hypobetalipoproteinemia. Read More

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http://dx.doi.org/10.2169/internalmedicine.3737-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118388PMC

Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.

Authors:
Francine K Welty

Curr Opin Lipidol 2020 Apr;31(2):49-55

Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Purpose Of Review: Several mutations in the apolipoprotein (apo) B, proprotein convertase subtilisin kexin 9 (PCSK9) and microsomal triglyceride transfer protein genes result in low or absent levels of apoB and LDL cholesterol (LDL-C) in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). Mutations in the angiopoietin-like protein 3 ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). Clinical manifestations range from none-to-severe, debilitating and life-threatening disorders. Read More

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http://dx.doi.org/10.1097/MOL.0000000000000663DOI Listing

Low LDL cholesterol-Friend or foe?

J Clin Lipidol 2019 May - Jun;13(3):367-373. Epub 2019 May 16.

Department of Pediatric Endocrinology, Cook Children's Medical Center, Ft Worth, TX, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jacl.2019.05.006DOI Listing
March 2020
2 Reads

N-Glycosylation Defects in Humans Lower Low-Density Lipoprotein Cholesterol Through Increased Low-Density Lipoprotein Receptor Expression.

Circulation 2019 07 23;140(4):280-292. Epub 2019 May 23.

Departments of Vascular Medicine (M.A.W.v.d.B., J.K., G.M.D.-T., E.S.G.S., A.G.H.), Amsterdam University Medical Centers, location AMC, The Netherlands.

Background: The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying patients with type I congenital disorders of glycosylation (CDGs) with defective N-glycosylation.

Methods: We studied 29 patients with the 2 most prevalent types of type I CDG, ALG6 (asparagine-linked glycosylation protein 6)-deficiency CDG and PMM2 (phosphomannomutase 2)-deficiency CDG, and 23 first- and second-degree relatives with a heterozygous mutation and measured plasma cholesterol levels. Read More

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036484DOI Listing
July 2019
27 Reads

Rare Protein-Truncating Variants in APOB, Lower Low-Density Lipoprotein Cholesterol, and Protection Against Coronary Heart Disease.

Circ Genom Precis Med 2019 05;12(5):e002376

Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (A.V.K., M.C., S.K.).

Background Familial hypobetalipoproteinemia is a genetic disorder caused by rare protein-truncating variants (PTV) in the gene encoding APOB (apolipoprotein B), the major protein component of LDL (low-density lipoprotein) and triglyceride-rich lipoprotein particles. Whether heterozygous APOB deficiency is associated with decreased risk for coronary heart disease (CHD) is uncertain. We combined family-based and large scale gene-sequencing to characterize the association of rare PTVs in APOB with circulating LDL-C (LDL cholesterol), triglycerides, and risk for CHD. Read More

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http://dx.doi.org/10.1161/CIRCGEN.118.002376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044908PMC
May 2019
34 Reads

Extremely low levels of low-density lipoprotein potentially suggestive of familial hypobetalipoproteinemia: A separate phenotype of NAFLD?

J Clin Lipidol 2019 May - Jun;13(3):425-431. Epub 2019 Feb 14.

Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati School of Medicine, Cincinnati, OH, USA.

Background: Low-density lipoprotein cholesterol (LDL-C) levels below 50 mg/dL may suggest familial hypobetalipoproteinemia, particularly in patients with hepatic steatosis. The prevalence of hypobetalipoproteinemia in cohorts with nonalcoholic fatty liver disease (NAFLD) is not known, and it is not clear whether the severity of liver disease of these patients is different. The objective of this study was to address these questions in a large pediatric NAFLD cohort. Read More

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http://dx.doi.org/10.1016/j.jacl.2019.02.002DOI Listing
May 2020
9 Reads

Molecular analysis of APOB, SAR1B, ANGPTL3, and MTTP in patients with primary hypocholesterolemia in a clinical laboratory setting: Evidence supporting polygenicity in mutation-negative patients.

Atherosclerosis 2019 04 11;283:52-60. Epub 2019 Feb 11.

Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica - IIB Sant Pau, Barcelona, Spain. Electronic address:

Background And Aims: Primary hypobetalipoproteinemia is generally considered a heterogenic group of monogenic, inherited lipoprotein disorders characterized by low concentrations of LDL cholesterol and apolipoprotein B in plasma. Lipoprotein disorders include abetalipoproteinemia, familial hypobetalipoproteinemia, chylomicron retention disease, and familial combined hypolipidemia. Our aim was to review and analyze the results of the molecular analysis of hypolipidemic patients studied in our laboratory over the last 15 years. Read More

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http://dx.doi.org/10.1016/j.atherosclerosis.2019.01.036DOI Listing
April 2019
5 Reads

Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study.

Lipids Health Dis 2018 Nov 6;17(1):249. Epub 2018 Nov 6.

CHU Nantes, Service d'Addictologie et de Psychiatrie, F-44000, Nantes, France.

Background: Hypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders. Read More

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https://lipidworld.biomedcentral.com/articles/10.1186/s12944
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http://dx.doi.org/10.1186/s12944-018-0892-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220563PMC
November 2018
30 Reads

Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women.

Circulation 2018 02;137(8):820-831

Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, the Netherlands (J.-W.B., A.R., P.L., J.A.K.)

Background: Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in cardiovascular trials and research. This study aims at a better understanding of lifestyle and genetic factors that affect LDL-C in young women. Read More

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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032479DOI Listing
February 2018
52 Reads

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels.

PLoS One 2017 16;12(10):e0186446. Epub 2017 Oct 16.

Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: Screening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels.

Methods: Among 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were ≤1 percentile (48 mg/dL) of Korean population, were analyzed. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186446PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643101PMC
November 2017
128 Reads

Threshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins.

J Clin Endocrinol Metab 2017 09;102(9):3340-3348

Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon 97239.

Context: Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Read More

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http://academic.oup.com/jcem/article/102/9/3340/3869385/Thre
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http://dx.doi.org/10.1210/jc.2016-4043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587068PMC
September 2017
48 Reads

Low-Density Lipoprotein Cholesterol (LDL-C): How Low?

Authors:
Thomas F Whayne

Curr Vasc Pharmacol 2017 ;15(4):374-379

Wethington Building, 900 South Limestone Street, Lexington, KY 40536-0200. United States.

Low-density lipoprotein cholesterol (LDL-C) is a well-established major cardiovascular (CV) risk factor supported by clinical evidence showing decreased atherosclerotic disease events when LDL-C is therapeutically lowered. A reasonable approach is to tailor each patient's LDL-C target level depending on the initial LDL-C level and the perceived risk. Multiple clinical entities such as the newborn, hypobetalipoproteinemia, proprotein convertase subtilisin/kexin type 9 (PCSK9) missense mutations, and an unexpected excess response to a statin or other medications, are associated with very low LDL-C levels in otherwise healthy individuals. Read More

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http://www.eurekaselect.com/150431/article
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http://dx.doi.org/10.2174/1570161115666170227102708DOI Listing
April 2018
6 Reads

Association between familial hypobetalipoproteinemia and the risk of diabetes. Is this the other side of the cholesterol-diabetes connection? A systematic review of literature.

Acta Diabetol 2017 Feb 2;54(2):111-122. Epub 2016 Nov 2.

Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.

Statin therapy is beneficial in reducing LDL cholesterol (LDL-C) levels and cardiovascular events, but it is associated with the risk of incident diabetes mellitus (DM). Familial hypercholesterolemia (FH) is characterized by genetically determined high levels of plasma LDL-C and a low prevalence of DM. LDL-C levels seem then inversely correlated with prevalence of DM. Read More

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http://dx.doi.org/10.1007/s00592-016-0931-4DOI Listing
February 2017
12 Reads

 The relation of fibrosis stage with nutritional deficiencies and bioelectrical impedance analysis of body composition in patients with chronic hepatitis C.

Ann Hepatol 2016 Jul-Aug;15(4):492-500

Services of Gastroenterology Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Department of Medicine, Medical School, Universidad Complutense, Madrid, Spain.

Unlabelled:  Background. Nutritional deficiencies may aggravate the course of chronic hepatitis C (CHC). Our aim has been to perform a comprehensive analysis of body composition and nutritional deficiencies in CHC patients in non-cirrhotic and compensated cirrhotic stages to correlate the detected deficiencies with the fibrosis stage. Read More

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February 2017
58 Reads

Novel APOB missense variants, A224T and V925L, in a black South African woman with marked hypocholesterolemia.

J Clin Lipidol 2016 May-Jun;10(3):604-9. Epub 2016 Feb 16.

School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital, Perth, Western Australia, Australia. Electronic address:

Background: One genetic cause of markedly low plasma concentrations of apolipoprotein (apo) B and low density lipoprotein (LDL)-cholesterol is familial hypobetalipoproteinemia.

Objective: We aimed to determine the molecular basis for the marked hypocholesterolemia consistent with heterozygous familial hypobetalipoproteinemia in a black female subject of Xhosa lineage.

Methods: Coding regions of APOB, MTTP, PCSK9,ANGPTL3, SAR1B and APOC3 were sequenced, and APOE was genotyped. Read More

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http://dx.doi.org/10.1016/j.jacl.2016.01.006DOI Listing
October 2017
25 Reads
1 Citation

Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia.

Atherosclerosis 2016 07 11;250:52-6. Epub 2016 Apr 11.

INSERM, UMR1087, l'institut du thorax, Nantes, F-44000, France; CNRS, UMR 6291, Nantes, F-44000, France; Université de Nantes, Nantes, F-44000, France; CHU Nantes, l'institut du Thorax, Nantes, F-44000, France; CIC Thorax, CHU Nantes, l'institut du Thorax, Nantes, F-44000, France. Electronic address:

Background And Aims: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species.

Methods: Here, we applied targeted enrichment and next-generation sequencing (NGS) on a panel of three FHBL genes and two abetalipoproteinemia genes (APOB, PCSK9, ANGPTL3, MTTP and SAR1B). Read More

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http://dx.doi.org/10.1016/j.atherosclerosis.2016.04.010DOI Listing
July 2016
70 Reads

Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia.

Dis Model Mech 2016 Jan 19;9(1):81-90. Epub 2015 Nov 19.

INSERM, UMR1087, L'institut du thorax, Nantes F-44000, France CNRS, UMR 6291, Nantes F-44000, France Université de Nantes, Nantes F-44000, France CHU Nantes, L'institut du thorax, CIC Endocrinology-Nutrition, Nantes F-44000, France.

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. Read More

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http://dmm.biologists.org/content/dmm/early/2015/11/19/dmm.0
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http://dmm.biologists.org/lookup/doi/10.1242/dmm.022277
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http://dx.doi.org/10.1242/dmm.022277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728336PMC
January 2016
59 Reads
4.973 Impact Factor

Update on the molecular biology of dyslipidemias.

Authors:
I Ramasamy

Clin Chim Acta 2016 Feb 4;454:143-85. Epub 2015 Nov 4.

Department of Biochemistry, Worcester Royal Hospital, Worcester, United Kingdom.

Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00098981153003
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http://dx.doi.org/10.1016/j.cca.2015.10.033DOI Listing
February 2016
38 Reads

Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.

J Clin Endocrinol Metab 2015 Nov 31;100(11):E1484-90. Epub 2015 Aug 31.

Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.

Context: Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB).

Objective: The objective was to examine the effect of heterozygous APOB L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism.

Methods: Plasma incremental area under the curve apoB-48 and apoB-48 kinetics were determined after ingestion of a standardized oral fat load using compartmental modeling. Read More

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http://dx.doi.org/10.1210/jc.2015-2731DOI Listing
November 2015
27 Reads
6.210 Impact Factor

Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.

Atherosclerosis 2015 Mar 19;239(1):209-17. Epub 2015 Jan 19.

Department of Pharmacology and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy; IRCCS Multimedica, Milano, Italy. Electronic address:

Objective: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5(th) percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. Read More

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http://dx.doi.org/10.1016/j.atherosclerosis.2015.01.014DOI Listing
March 2015
42 Reads

Contemporary aspects of the biology and therapeutic regulation of the microsomal triglyceride transfer protein.

Circ Res 2015 Jan;116(1):193-205

Department of Clinical Biochemistry, PathWest Laboratory Medicine WA (A.J.H., J.R.B.), School of Medicine and Pharmacology (A.J.H., J.R.B., G.F.W.), School of Pathology and Laboratory Medicine (A.J.H), and Lipid Disorders Clinic, Cardiovascular Medicine (J.R.B., G.F.W), Royal Perth Hospital, University of Western Australia, Perth, Western Australia, Australia.

The microsomal triglyceride transfer protein (MTP), the product of the MTTP gene, is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins, but when defective causes abetalipoproteinemia. Abetalipoproteinemia is a rare autosomal recessive disorder characterized by the inability to produce chylomicrons or very low-density lipoproteins, with the absence of apolipoprotein B-containing lipoproteins in the circulation. Knowledge of the molecular basis for abetalipoproteinemia has led to the development of therapies for dyslipidemia that inhibit MTP. Read More

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http://dx.doi.org/10.1161/CIRCRESAHA.116.304637DOI Listing
January 2015
17 Reads
3 Citations
11.020 Impact Factor

Hypobetalipoproteinemia and abetalipoproteinemia.

Authors:
Francine K Welty

Curr Opin Lipidol 2014 Jun;25(3):161-8

Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Purpose Of Review: Several mutations in the apoB, proprotein convertase subtilisin/kexin type 9 (PCSK9), and MTP genes result in low or absent levels of apoB and LDL-cholesterol in plasma, which cause familial hypobetalipoproteinemia and abetalipoproteinemia. Mutations in the ANGPTL3 gene cause familial combined hypolipidemia. Clinical manifestations range from none to severe, debilitating, and life-threatening disorders. Read More

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http://pdfs.journals.lww.com/co-lipidology/2014/06000/Hypobe
Web Search
http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:land
Publisher Site
http://dx.doi.org/10.1097/MOL.0000000000000072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465983PMC
June 2014
28 Reads

How low an LDL-C should we go with statin therapy?

Authors:
William J Kostis

Curr Atheroscler Rep 2014 Feb;16(2):388

Cardiology Division, Massachusetts General Hospital, 55 Fruit St., GRB-800, Boston, MA, 02114, USA,

There is evidence from epidemiology, pathophysiology, and clinical trials that high LDL cholesterol levels cause atherosclerotic heart disease. Current guidelines recommend an LDL cholesterol target of 70 mg/dL for patients at high or very high risk. The risk imposed by LDL cholesterol is modulated by the presence of additional risk factors such as age, smoking, and indices of inflammation. Read More

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http://link.springer.com/10.1007/s11883-013-0388-7
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http://dx.doi.org/10.1007/s11883-013-0388-7DOI Listing
February 2014
8 Reads

LDL but not HDL increases adiponectin release of primary human adipocytes.

Exp Mol Pathol 2013 Dec 22;95(3):325-9. Epub 2013 Oct 22.

Department of Internal Medicine I, Regensburg University Hospital, D-93042 Regensburg, Germany.

Adipocytes in obesity have inappropriately low cholesterol while adiponectin release is reduced. Cholesterol shortage may contribute to low adiponectin and 3T3-L1 cells treated with lovastatin have diminished adiponectin in cell supernatants. LDL and HDL deliver cholesterol to adipocytes. Read More

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http://dx.doi.org/10.1016/j.yexmp.2013.10.002DOI Listing
December 2013
42 Reads

Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene.

Gene 2013 Nov 31;531(1):92-6. Epub 2013 Aug 31.

Unidad de Lípidos, Unidad de Gestión Clínica de Medicina Interna, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Malaga, Spain.

Extremely low LDL-cholesterol concentrations are very unusual and generally related with comorbidities accompanying malnutrition. Less frequently low LDL-cholesterol levels result from mutations in the APOB, PCSK9, ANGPTL3, SAR1B and MTTP genes (primary hypobetalipoproteinemia). We investigated three patients with plasma LDL-cholesterol levels below the fifth percentile of the Spanish population. Read More

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http://dx.doi.org/10.1016/j.gene.2013.08.049DOI Listing
November 2013
6 Reads

Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids.

Arterioscler Thromb Vasc Biol 2013 Jul 9;33(7):1706-13. Epub 2013 May 9.

Public Health Genomics Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland.

Objective: Angiopoietin-like 3 (Angptl3) is a regulator of lipoprotein metabolism at least by inhibiting lipoprotein lipase activity. Loss-of-function mutations in ANGPTL3 cause familial combined hypolipidemia through an unknown mechanism.

Approach And Results: We compared lipolytic activities, lipoprotein composition, and other lipid-related enzyme/lipid transfer proteins in carriers of the S17X loss-of-function mutation in ANGPTL3 and in age- and sex-matched noncarrier controls. Read More

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http://dx.doi.org/10.1161/ATVBAHA.113.301397DOI Listing
July 2013
26 Reads

Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene.

Diagn Pathol 2013 Apr 4;8:54. Epub 2013 Apr 4.

Background: Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder of lipid metabolism characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal triglyceride transfer protein (MTP; OMIM 157147). In the present study we investigated two unrelated Tunisian patients, born from consanguineous marriages, with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Read More

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http://diagnosticpathology.biomedcentral.com/articles/10.118
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http://dx.doi.org/10.1186/1746-1596-8-54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632489PMC
April 2013
37 Reads

Exon skipping of hepatic APOB pre-mRNA with splice-switching oligonucleotides reduces LDL cholesterol in vivo.

Mol Ther 2013 Mar 15;21(3):602-9. Epub 2013 Jan 15.

Institute for Liver and Digestive Health, UCL, London, UK.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by extremely high levels of plasma low-density lipoprotein (LDL), due to defective LDL receptor-apolipoprotein B (APOB) binding. Current therapies such as statins or LDL apheresis for homozygous FH are insufficiently efficacious at lowering LDL cholesterol or are expensive. Treatments that target APOB100, the structural protein of LDL particles, are potential therapies for FH. Read More

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http://linkinghub.elsevier.com/retrieve/pii/S152500161630629
Publisher Site
http://dx.doi.org/10.1038/mt.2012.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589156PMC
March 2013
43 Reads
8 Citations
6.230 Impact Factor

Recent developments in the genetics of LDL deficiency.

Curr Opin Lipidol 2013 Apr;24(2):111-5

Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Australia.

Purpose Of Review: Inherited diseases of lipoprotein metabolism may give rise to marked hypocholesterolemia with low or absent levels of LDL, depending on the gene involved and mode of inheritance of the condition, together with the severity of the mutation or mutations present. In this review, we discuss the recent developments in the genetics of LDL deficiency.

Recent Findings: Carriers of a single loss-of-function variant in ANGPTL3 have reduced LDL-cholesterol and triglyceride concentrations, whereas homozygotes have markedly reduced LDL-cholesterol, triglyceride and HDL-cholesterol concentrations, a recessive form of hypocholesterolemia designated as familial combined hypolipidemia. Read More

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http://dx.doi.org/10.1097/MOL.0b013e32835ca0d9DOI Listing
April 2013
20 Reads
2 Citations
5.660 Impact Factor

Chronic adrenal failure and hypergonadotropic hypogonadism in a patient with abetalipoproteinemia.

Authors:
R Krysiak B Okopie

Eur Rev Med Pharmacol Sci 2012 Oct;16 Suppl 4:95-7

Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.

Introduction: Abetalipoproteinemia is a rare inherited disorder characterized by very low plasma levels of cholesterol and triglycerides, secondary to a dramatic decrease in apolipoprotein B-containing lipoproteins, which is induced by a mutation in the microsomal triglyceride transfer protein gene.

Case: In our paper, we describe an atypical clinical manifestation of this condition in a young man, which included the presence of hypogonadism and chronic adrenal failure. We connect the development of both endocrine disorders with very low plasma levels of cholesterol, which is uptaken by the gonads and adrenal cortex and used as a substrate for steroidogenesis, accentuated by carbamazepine treatment. Read More

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October 2012
5 Reads

A randomized controlled trial to evaluate the effectiveness of CouPLES: a spouse-assisted lifestyle change intervention to improve low-density lipoprotein cholesterol.

Prev Med 2013 Jan 9;56(1):46-52. Epub 2012 Nov 9.

Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC, USA.

Objective: This randomized controlled trial evaluated the effectiveness of a telephone-delivered, spouse-assisted lifestyle intervention to reduce patient LDL-C.

Method: From 2007 to 2010, 255 outpatients with LDL-C>76 mg/dL and their spouses from the Durham Veterans Affairs Medical Center were randomized to intervention or usual care. The intervention comprised nine monthly goal-setting telephone calls to patients and support planning calls to spouses. Read More

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http://dx.doi.org/10.1016/j.ypmed.2012.11.001DOI Listing
January 2013
35 Reads

Familial hypobetalipoproteinemia-induced nonalcoholic steatohepatitis.

Case Rep Gastroenterol 2012 May 3;6(2):429-37. Epub 2012 Jul 3.

Divisions of Gastroenterology, University of British Columbia, Vancouver, B.C.

Familial hypobetalipoproteinemia (FHBL) is a rare genetic disorder of lipid metabolism that is associated with abnormally low serum levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. It is an autosomal co-dominant disorder, and depending on zygosity, the clinical manifestations may vary from none to neurological, endocrine, hematological or liver dysfunction. Nonalcoholic fatty liver disease is common in persons with FHBL, however progression to nonalcoholic steatohepatitis is unusual. Read More

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https://www.karger.com/Article/FullText/339761
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http://dx.doi.org/10.1159/000339761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398101PMC
May 2012
42 Reads

Assessment of low-density lipoprotein targets.

Authors:
Thomas F Whayne

Angiology 2013 Aug 25;64(6):411-6. Epub 2012 Jun 25.

Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY 40536, USA.

The clinical importance of lowering of total cholesterol and low-density lipoprotein cholesterol (LDL-C) to decrease cardiovascular (CV) risk has been verified over many years starting with significant support in 1984 of the then previous lipid hypothesis. Significant support of this hypothesis began that year with publication of the Lipid Research Clinic study. Since then, multiple other studies including outcomes studies have established the value of LDL-C reduction in decreasing CV risk. Read More

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http://dx.doi.org/10.1177/0003319712451115DOI Listing
August 2013
10 Reads

Novel missense variants in LCAT and APOB genes in an Italian kindred with familial lecithin:cholesterol acyltransferase deficiency and hypobetalipoproteinemia.

J Clin Lipidol 2012 May-Jun;6(3):244-50. Epub 2012 Jan 28.

Center E. Grossi Paoletti, Department of Pharmacological Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy.

Background: Lecithin:cholesterol acyltransferase (LCAT) is responsible for cholesterol esterification in plasma. Mutations of LCAT gene cause familial LCAT deficiency, a metabolic disorder characterized by hypoalphalipoproteinemia. Apolipoprotein B (apoB) is the main protein component of very-low-density lipoproteins and low-density lipoprotein (LDL). Read More

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http://dx.doi.org/10.1016/j.jacl.2012.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361081PMC
September 2012
51 Reads

Low rate of production of apolipoproteins B100 and AI in 2 patients with Anderson disease (chylomicron retention disease).

Arterioscler Thromb Vasc Biol 2012 Jun 22;32(6):1520-5. Epub 2012 Mar 22.

INSERM UMR 1087/CNRS UMR 6291 and CRNH Nantes, IRT-UN, Nantes, France.

Objective: Anderson disease is a rare inherited lipid malabsorption syndrome associated with hypocholesterolemia and linked to SAR1B mutations. The aim of this article was to analyze the mechanisms responsible for the low plasma apolipoprotein Apo-B100 and Apo-AI in 2 patients with Anderson disease.

Methods And Results: A primed constant infusion of (13)C-leucine was administered for 14 hours to determine the kinetics of lipoproteins. Read More

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http://dx.doi.org/10.1161/ATVBAHA.112.245076DOI Listing
June 2012
20 Reads

Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia.

J Lipid Res 2012 Mar 11;53(3):548-55. Epub 2012 Jan 11.

Hospices Civils de Lyon, Centre de Biologie et de Pathologie Est, Département de Biochimie et Biologie Moléculaire, Bron F-69677, France. mathilde.di-fi

Abetalipoproteinemia (ABL) is an inherited disease characterized by the defective assembly and secretion of apolipoprotein B-containing lipoproteins caused by mutations in the microsomal triglyceride transfer protein large subunit (MTP) gene (MTTP). We report here a female patient with an unusual clinical and biochemical ABL phenotype. She presented with severe liver injury, low levels of LDL-cholesterol, and subnormal levels of vitamin E, but only mild fat malabsorption and no retinitis pigmentosa or acanthocytosis. Read More

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http://dx.doi.org/10.1194/jlr.M020024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276478PMC
March 2012
15 Reads

Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation.

Clin Chim Acta 2012 Mar 29;413(5-6):552-5. Epub 2011 Nov 29.

Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.

Background: Familial hypobetalipoproteinemia (FHBL), characterized by extremely low levels of plasma apolipoprotein (apo) B and cholesterol associated with low-density lipoproteins (LDLc), is considered to be an autosomal co-dominant disorder of heterogeneous origin. The main genetic disorder associated with FHBL consists of mutations in the APOB gene, while other less frequent forms are associated with mutations in NPC1L1, PCSK9, a still unidentified gene in 3p21.1-22 and, more recently, in ANGPTL3. Read More

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http://dx.doi.org/10.1016/j.cca.2011.11.020DOI Listing
March 2012
19 Reads

Characterization of three kindreds with familial combined hypolipidemia caused by loss-of-function mutations of ANGPTL3.

Circ Cardiovasc Genet 2012 Feb 7;5(1):42-50. Epub 2011 Nov 7.

Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, Genoa, Italy.

Background: Angiopoietin-like protein 3 (ANGPTL3) affects lipid metabolism by inhibiting the activity of lipoprotein and endothelial lipases. Angptl3 knockout mice have marked hypolipidemia, and heterozygous carriers of ANGPLT3, loss-of-function mutations were found among individuals in the lowest quartile of plasma triglycerides in population studies. Recently, 4 related individuals with primary hypolipidemia were found to be compound heterozygotes for ANGPTL3 loss-of-function mutations. Read More

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http://dx.doi.org/10.1161/CIRCGENETICS.111.960674DOI Listing
February 2012
23 Reads

Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum.

Adv Clin Chem 2011 ;54:81-107

Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5th percentile of the distribution in the population. HBL are defined as primary or secondary according to the underlying causes. Primary monogenic HBL are caused by mutations in several known genes (APOB, PCSK9, MTP, SARA2) or mutations in genes not yet identified. Read More

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September 2011
41 Reads

New lipid modulating drugs: the role of microsomal transport protein inhibitors.

Curr Pharm Des 2011 ;17(9):943-9

Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.

Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. Read More

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http://dx.doi.org/10.2174/138161211795428768DOI Listing
December 2011
9 Reads

Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia.

N Engl J Med 2010 Dec 13;363(23):2220-7. Epub 2010 Oct 13.

Cardiovascular Research Center, Massachusetts General Hospital, and Department of Medicine, Boston University School of Public Health, Boston, MA 02114, USA.

We sequenced all protein-coding regions of the genome (the "exome") in two family members with combined hypolipidemia, marked by extremely low plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. These two participants were compound heterozygotes for two distinct nonsense mutations in ANGPTL3 (encoding the angiopoietin-like 3 protein). ANGPTL3 has been reported to inhibit lipoprotein lipase and endothelial lipase, thereby increasing plasma triglyceride and HDL cholesterol levels in rodents. Read More

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http://dx.doi.org/10.1056/NEJMoa1002926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008575PMC
December 2010
64 Reads

Hypocholesterolemia.

Curr Vasc Pharmacol 2011 Mar;9(2):200-12

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

Hypocholesterolemia is defined as total cholesterol (TC) and low density cholesterol (LDL-C) levels below the 5(th) percentile of the general population adjusted for age, gender and race. Hypocholesterolemia may be attributed to inherited disorders or several secondary causes. Inherited forms of hypocholesterolemia consist of a group of rare diseases. Read More

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http://dx.doi.org/10.2174/157016111794519354DOI Listing
March 2011
18 Reads

Familial hypobetalipoproteinemia: early neurological, hematological, and ocular manifestations in two affected twins responding to vitamin supplementation.

Curr Opin Pediatr 2009 Dec;21(6):824-7

Department of Pediatric Medicine, Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Familial hypobetalipoproteinemia is a disorder of lipid metabolism characterized by extremely low plasma levels of apolipoprotein B as well as low levels of total and low-density lipoprotein cholesterol. We report the case of impairment of retinal function and diffuse pain in both legs often related to physical activity, as well as the presence of acanthocytosis on peripheral blood smear. Neurophysiological studies suggested dysfunction of the thin myelinated (A) and unmyelinated (C) fibers, in spite of preserved A fiber function, which has not been previously described in this condition. Read More

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http://dx.doi.org/10.1097/MOP.0b013e32833252f2DOI Listing
December 2009
10 Reads

PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia.

Arterioscler Thromb Vasc Biol 2009 Dec 17;29(12):2191-7. Epub 2009 Sep 17.

INSERM, U915, Nantes F-44000, France.

Objective: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central player in the regulation of cholesterol homeostasis, increasing the low-density lipoprotein (LDL) receptor degradation. Our study aimed at exploring the pathogenic consequences in vivo and in vitro of a PCSK9 prodomain mutation found in a family with hypobetalipoproteinemia (FHBL).

Methods And Results: A white 49-year-old diabetic man had profound FBHL (LDLC: 16 mg/dL) whereas his daughter and sister displayed a milder phenotype (LDLC 44 mg/dL and 57 mg/dL, respectively), all otherwise healthy with a normal liver function. Read More

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http://dx.doi.org/10.1161/ATVBAHA.109.194191DOI Listing
December 2009
38 Reads
18 Citations
6.000 Impact Factor

Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation.

Liver Transpl 2009 Jul;15(7):806-9

Department of Surgery and Medical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Familial hypobetalipoproteinemia (FHBL) is one of the causes of nonalcoholic steatohepatitis (NASH) and a codominant disorder. Patients heterozygous for FHBL may be asymptomatic, although they demonstrate low plasma levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Here we report a nonobese 54-year-old man with decompensated liver cirrhosis who underwent living donor liver transplantation with his son as the donor. Read More

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http://dx.doi.org/10.1002/lt.21766DOI Listing
July 2009
10 Reads

Hypobetalipoproteinaemia secondary to chronic hepatitis C virus infection in a patient with familial hypercholesterolaemia.

Ann Clin Biochem 2009 Sep 1;46(Pt 5):420-2. Epub 2009 Jun 1.

Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, WA 6847, Australia.

Familial hypercholesterolaemia (FH) is a common genetic disorder characterized by high plasma low-density lipoprotein (LDL)-cholesterol and premature coronary artery disease. Many factors, such as illness, high-dose statin therapy or a strict vegan diet can cause hypobetalipoproteinaemia (HBL). The more common secondary causes of HBL in the hospital setting include cachexia, intestinal malabsorption, malnutrition, severe liver disease and hyperthyroidism. Read More

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http://dx.doi.org/10.1258/acb.2009.009004DOI Listing
September 2009
46 Reads
1 Citation
2.080 Impact Factor

Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease.

Hum Mutat 2009 Apr;30(4):520-9

Institut Nationale de la Santé et de la Recherche Médicale (INSERM), U781, Paris, France.

Hypercholesterolemia is one of the major causes of coronary heart disease (CHD). The genes encoding the low-density lipoprotein receptor and its ligand apolipoprotein B, have been the two genes classically implicated in autosomal dominant hypercholesterolemia (ADH). Our discovery in 2003 of the first mutations of the proprotein convertase subtilisin kexin 9 gene (PCSK9) causing ADH shed light on an unknown actor in cholesterol metabolism that since then has been extensively investigated. Read More

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http://dx.doi.org/10.1002/humu.20882DOI Listing
April 2009
9 Reads

Functional analysis of two novel splice site mutations of APOB gene in familial hypobetalipoproteinemia.

Mol Genet Metab 2009 Feb 11;96(2):66-72. Epub 2008 Dec 11.

Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, I-41100 Modena, Italy.

Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by reduced plasma levels of low density lipoprotein cholesterol (LDL-C) and its protein constituent apolipoprotein B (apoB), which may be due to mutations in APOB gene, mostly located in the coding region of this gene. We report two novel APOB gene mutations involving the acceptor splice site of intron 11 (c.1471-1G>A) and of intron 23 (c. Read More

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http://dx.doi.org/10.1016/j.ymgme.2008.10.016DOI Listing
February 2009
37 Reads