Related Experiment Video

Updated: Dec 31, 2025

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

8.4K

The familial hypercholesterolaemia phenotype: Monogenic familial hypercholesterolaemia, polygenic

Cibelle Mariano1,2, Ana Catarina Alves1,2, Ana Margarida Medeiros1,2

  • 1Cardiovascular Research Group, Research and Development Unit, Department of Health Promotion and Chronic Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal.

Clinical Genetics
|January 2, 2020
PubMed

Insights

Genetic testing identified a cause for familial hypercholesterolaemia (FH) in 69% of Portuguese patients. This included FH-causing mutations in 39% and polygenic hypercholesterolaemia in 29%, highlighting the need for comprehensive genetic evaluation.

Area of Science:

  • Genetics
  • Cardiology
  • Biochemistry

Background:

  • Familial hypercholesterolaemia (FH) is a monogenic disorder leading to high LDL-C and increased cardiovascular risk.
  • Genetic variants are identified in only 40-50% of clinically diagnosed FH cases globally.
  • Comprehensive genetic characterization is crucial for understanding FH etiology.

Purpose of the Study:

  • To determine the genetic causes of the FH phenotype in Portuguese patients.
  • To investigate both monogenic and polygenic hypercholesterolaemia in a clinical FH cohort.
  • To assess the diagnostic yield of genetic testing in FH.

Main Methods:

  • Analysis of 731 index patients meeting Simon Broome criteria between 1999-2017.
  • Sanger sequencing of key genes (LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8).
  • Validation of a 6-SNP genetic risk score (GRS) for polygenic hypercholesterolaemia.

Main Results:

  • FH-causing mutations identified in 39% of patients (94% in LDLR, 5% APOB, 1% PCSK9).
  • Polygenic hypercholesterolaemia identified in at least 29% of patients.
  • A genetic cause for the FH phenotype was established in 69% of the cohort.

Conclusions:

  • A significant proportion of FH phenotypes in Portugal are attributable to monogenic mutations or polygenic hypercholesterolaemia.
  • Comprehensive genetic investigation, including polygenic risk scores, is essential for accurate FH diagnosis.
  • Identifying the genetic basis of FH is critical for appropriate patient management and cardiovascular risk reduction.

Keywords:
familial hypercholesterolaemiagenetic risk scoremonogenic dyslipidaemiaphenocopiespolygenic hypercholesterolaemia

More Related Videos

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

14.0K
Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation06:47

Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation

Published on: January 28, 2021

12.3K

Related Concept Videos

Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.3K
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
1.2K
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
311
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.1K
Polygenic Traits01:18

Polygenic Traits

When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...
68.7K
Blood Studies for Cardiovascular System III: Serum Lipid Profile01:25

Blood Studies for Cardiovascular System III: Serum Lipid Profile

Understanding serum lipids is crucial for maintaining cardiovascular health and preventing heart disease and stroke.
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
525