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Questions and Answers
A genetic disorder characterised by high cholesterol levels, specifically very high levels of low density lipoprotein (LDL aka 'bad' cholesterol) in the blood is known as familial ______.
A genetic disorder characterised by high cholesterol levels, specifically very high levels of low density lipoprotein (LDL aka 'bad' cholesterol) in the blood is known as familial ______.
hypercholesterolemia
Angina pectoris, which is a symptom of FH, is described as ______ pain or tightness in the chest.
Angina pectoris, which is a symptom of FH, is described as ______ pain or tightness in the chest.
chest
The LDLR gene encodes a low density lipoprotein ______ responsible for cholesterol uptake.
The LDLR gene encodes a low density lipoprotein ______ responsible for cholesterol uptake.
receptor
Statins work by decreasing cholesterol ______, thereby reducing cholesterol absorption after it leaves the liver.
Statins work by decreasing cholesterol ______, thereby reducing cholesterol absorption after it leaves the liver.
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Mutations in the LDLR gene can lead to ______ cholesterol levels and are associated with an increased risk of heart disease.
Mutations in the LDLR gene can lead to ______ cholesterol levels and are associated with an increased risk of heart disease.
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ApoB-100 acts as a ligand for LDLRs, allowing LDLs to ______ effectively to liver cells.
ApoB-100 acts as a ligand for LDLRs, allowing LDLs to ______ effectively to liver cells.
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The prevalence of the heterozygous state (HeFH) for FH is 1 in ______ to 1 in 500.
The prevalence of the heterozygous state (HeFH) for FH is 1 in ______ to 1 in 500.
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In Quebec, the prevalence of FH populations is 1 in ______.
In Quebec, the prevalence of FH populations is 1 in ______.
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The family history of ______ is a key sign for diagnosing FH.
The family history of ______ is a key sign for diagnosing FH.
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The enzyme encoded by the PCSK9 gene directs LDLR for ______ rather than recycling.
The enzyme encoded by the PCSK9 gene directs LDLR for ______ rather than recycling.
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Bile acid sequestrants help to reduce LDL levels by increasing bile acid ______.
Bile acid sequestrants help to reduce LDL levels by increasing bile acid ______.
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Individuals with the homozygous state of FH have ______ LDL cholesterol levels compared to those with the heterozygous state.
Individuals with the homozygous state of FH have ______ LDL cholesterol levels compared to those with the heterozygous state.
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The mutation hotspot for ApoB is found in ______ 26.
The mutation hotspot for ApoB is found in ______ 26.
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Treatment for FH includes reducing the intake of carbohydrates and ______ fatty acids.
Treatment for FH includes reducing the intake of carbohydrates and ______ fatty acids.
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The autosomal dominant inheritance pattern of FH means that a single ______ can result in the disorder.
The autosomal dominant inheritance pattern of FH means that a single ______ can result in the disorder.
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The presence of ______ mutations in the LDLR gene has been linked to increased LDL levels.
The presence of ______ mutations in the LDLR gene has been linked to increased LDL levels.
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What is the primary consequence of Familial Hypercholesterolemia?
What is the primary consequence of Familial Hypercholesterolemia?
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Which gene is responsible for the majority of Familial Hypercholesterolemia cases?
Which gene is responsible for the majority of Familial Hypercholesterolemia cases?
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How does the LDL receptor (LDLR) impact cholesterol levels in the bloodstream?
How does the LDL receptor (LDLR) impact cholesterol levels in the bloodstream?
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What is a common symptom associated with Familial Hypercholesterolemia?
What is a common symptom associated with Familial Hypercholesterolemia?
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What lifestyle change is commonly recommended for individuals with Familial Hypercholesterolemia?
What lifestyle change is commonly recommended for individuals with Familial Hypercholesterolemia?
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Which of the following mutations is most commonly associated with Familial Hypercholesterolemia?
Which of the following mutations is most commonly associated with Familial Hypercholesterolemia?
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What is the worldwide prevalence of heterozygous Familial Hypercholesterolemia?
What is the worldwide prevalence of heterozygous Familial Hypercholesterolemia?
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Which chromosome is the LDLR gene located on?
Which chromosome is the LDLR gene located on?
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What is the consequence of gain-of-function mutations in the PCSK9 gene?
What is the consequence of gain-of-function mutations in the PCSK9 gene?
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Which apolipoprotein isoform is primarily expressed in the liver?
Which apolipoprotein isoform is primarily expressed in the liver?
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What is the prevalence of homozygous familial hypercholesterolemia (HoFH) in the general population?
What is the prevalence of homozygous familial hypercholesterolemia (HoFH) in the general population?
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What is the effect of loss-of-function mutations in the ApoB gene?
What is the effect of loss-of-function mutations in the ApoB gene?
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Which population shows a higher incidence of familial hypercholesterolemia?
Which population shows a higher incidence of familial hypercholesterolemia?
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What inheritance pattern is observed in familial hypercholesterolemia?
What inheritance pattern is observed in familial hypercholesterolemia?
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Which of the following factors contributes to the founder effect in the Quebec population?
Which of the following factors contributes to the founder effect in the Quebec population?
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What role does PCSK9 play in the regulation of LDL receptors?
What role does PCSK9 play in the regulation of LDL receptors?
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Which gene is identified as responsible for the majority of Familial Hypercholesterolemia cases?
Which gene is identified as responsible for the majority of Familial Hypercholesterolemia cases?
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What is a characteristic of the LDL receptor (LDLR) that influences cholesterol levels?
What is a characteristic of the LDL receptor (LDLR) that influences cholesterol levels?
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What is the impact of gaining function mutations in the PCSK9 gene?
What is the impact of gaining function mutations in the PCSK9 gene?
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Which lifestyle change is generally NOT recommended for individuals with Familial Hypercholesterolemia?
Which lifestyle change is generally NOT recommended for individuals with Familial Hypercholesterolemia?
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In what way does Familial Hypercholesterolemia typically manifest early in affected individuals?
In what way does Familial Hypercholesterolemia typically manifest early in affected individuals?
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Which type of xanthoma is associated with Familial Hypercholesterolemia?
Which type of xanthoma is associated with Familial Hypercholesterolemia?
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What is the correct worldwide prevalence of heterozygous Familial Hypercholesterolemia?
What is the correct worldwide prevalence of heterozygous Familial Hypercholesterolemia?
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How is the incidence of Familial Hypercholesterolemia notably affected in the Quebec population?
How is the incidence of Familial Hypercholesterolemia notably affected in the Quebec population?
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What is the primary effect of loss-of-function mutations in the ApoB gene?
What is the primary effect of loss-of-function mutations in the ApoB gene?
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Which population group is NOT associated with a higher incidence of familial hypercholesterolemia?
Which population group is NOT associated with a higher incidence of familial hypercholesterolemia?
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What characterizes the phenotypic spectrum of homozygous familial hypercholesterolemia (HoFH) compared to heterozygous familial hypercholesterolemia (HeFH)?
What characterizes the phenotypic spectrum of homozygous familial hypercholesterolemia (HoFH) compared to heterozygous familial hypercholesterolemia (HeFH)?
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How do gain-of-function mutations in the PCSK9 gene affect LDL receptors?
How do gain-of-function mutations in the PCSK9 gene affect LDL receptors?
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Which apolipoprotein isoform is mainly expressed in the intestine?
Which apolipoprotein isoform is mainly expressed in the intestine?
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What is the main consequence of the founder effect in populations with familial hypercholesterolemia?
What is the main consequence of the founder effect in populations with familial hypercholesterolemia?
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Which factor could be considered a plausible reason for the variation in prevalence rates of FH between different populations?
Which factor could be considered a plausible reason for the variation in prevalence rates of FH between different populations?
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In familial hypercholesterolemia, what type of mutation in the LDLR gene primarily leads to hypercholesterolemia?
In familial hypercholesterolemia, what type of mutation in the LDLR gene primarily leads to hypercholesterolemia?
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Which gene accounts for the majority of Familial Hypercholesterolemia cases?
Which gene accounts for the majority of Familial Hypercholesterolemia cases?
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What type of dietary change is recommended for individuals with Familial Hypercholesterolemia?
What type of dietary change is recommended for individuals with Familial Hypercholesterolemia?
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What kind of xanthoma is commonly associated with Familial Hypercholesterolemia?
What kind of xanthoma is commonly associated with Familial Hypercholesterolemia?
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What is the main method by which LDL receptors affect cholesterol levels?
What is the main method by which LDL receptors affect cholesterol levels?
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Which population is noted for a higher incidence of Familial Hypercholesterolemia?
Which population is noted for a higher incidence of Familial Hypercholesterolemia?
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Which symptom is typically resistant to treatment in individuals with Familial Hypercholesterolemia?
Which symptom is typically resistant to treatment in individuals with Familial Hypercholesterolemia?
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What is the primary mechanism by which PCSK9 affects LDL receptors?
What is the primary mechanism by which PCSK9 affects LDL receptors?
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Which of the following mutations leads to increased LDL receptor degradation?
Which of the following mutations leads to increased LDL receptor degradation?
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Which population shows a notably higher prevalence of familial hypercholesterolemia?
Which population shows a notably higher prevalence of familial hypercholesterolemia?
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What is the typical impact of loss-of-function mutations in the ApoB gene?
What is the typical impact of loss-of-function mutations in the ApoB gene?
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What is the inheritance pattern of familial hypercholesterolemia?
What is the inheritance pattern of familial hypercholesterolemia?
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In familial hypercholesterolemia, what distinguishes homozygous from heterozygous patients concerning LDL cholesterol levels?
In familial hypercholesterolemia, what distinguishes homozygous from heterozygous patients concerning LDL cholesterol levels?
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Which exon in the ApoB gene is described as a mutational hotspot?
Which exon in the ApoB gene is described as a mutational hotspot?
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Study Notes
Familial Hypercholesterolemia (FH)
- A genetic disorder causing extremely high LDL ("bad") cholesterol and early cardiovascular disease.
- Difficult to diagnose: Often no obvious symptoms.
- High cholesterol that resists treatment: A key indicator.
- Family history is crucial: Premature heart attacks/strokes strongly suggest FH.
- Symptoms might include: Angina pectoris (chest pain), heart attack, or stroke at a younger age.
FH Genes and Mechanisms
- LDLR (Low-density lipoprotein receptor): This gene codes for a protein that removes cholesterol from the blood. High numbers of these receptors on cell surfaces remove cholesterol efficiently. Mutations reduce receptor function.
- LDLR mutations: Over 1,500 mutations in this gene are known.
- PCSK9 (Proprotein convertase subtilisin/kexin type 9): This gene codes for a protein that accelerates the degradation of LDLR, lowering the number of functional receptors.
- PCSK9 mutations: Over 150 mutations. These typically cause a "gain of function" effect.
- ApoB (Apolipoprotein B): Codes for a protein critical for LDL binding.
- ApoB mutations: Mutations in a specific region (exon 26) can lead to reduced binding and impaired LDL removal. In these cases it is often a "loss of function".
FH Inheritance and Prevalence
- Autosomal dominant: One copy of the mutated gene is sufficient to cause the disorder in many cases.
- Heterozygous (HeFH): One mutated copy, 1 in 200 to 1 in 500 people affected (varying by population).
- Homozygous (HoFH): Two mutated copies, 1 in 160,000 to 1 in 1,000,000 (varying by population).
- Homozygous individuals: Have significantly elevated LDL cholesterol than heterozygotes, almost double.
FH in Quebec
- Founder effect: Migration & isolation contributed to high FH prevalence.
- Specific LDLR mutation: A prominent 10kb deletion in the LDLR gene is common in French-Canadians.
- High prevalence in Quebec: 1 in 81 individuals carry this mutation; about 63% heterozygous for the deletion.
- Distinct mutations: 11 mutations account for over 90% of FH cases in the French-Canadian population. 5 of these account for 76%.
Treatment
- Dietary Restrictions: Reduce carbohydrates, saturated fats, and cholesterol intake.
- Bile acid sequestrants: Increase bile acid synthesis in the liver, reducing LDL levels.
- Statins: Reduce cholesterol synthesis, reducing cholesterol in the blood and absorption in the intestines.
Diagnosis
- Cascade screening: A cycle of testing relatives to expand potential diagnoses and identify potential cases.
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Description
This quiz explores Familial Hypercholesterolemia (FH), a genetic disorder characterized by high levels of LDL cholesterol and increased risk of early cardiovascular diseases. It covers symptoms, genetic mechanisms, and the importance of family history in diagnosis. Test your knowledge on the genetic factors and consequences associated with FH.
