Question

The Case of High Cholesterol

Part I

Renee and Karl have been married for six years, and have two active children, ages 2 and 5. The kids keep both parents busy, chasing the kids around and, recently, preparing the oldest child for kindergarten. In addition, both Renee and Karl work full time, so there isn’t a lot of free time to do things that are important to their health, like see the doctor for regular physicals. Both are healthy, so they haven’t been too worried.

Renee went for routine physical last week and had blood work drawn. (It had been three years since her last physical.) The doctor called during the day with some worrying results. After putting the kids to bed, Renee was ready to talk through the results with Karl. Karl, with a worried look on his face, asked what was up. Renee told him that her cholesterol levels were very high. In fact, her total cholesterol was 220. Her HDL was 20, and her LDL was 200. That information, combined with the fact that her father had passed away at a young age from a heart attack, worried the doctor…and Renee.

1. What are HDL and LDL?
   INSERT ANSWER

2. What is the normal role of cholesterol in the body? Do you need cholesterol? (Hint: Remember cell membranes.)
   INSERT ANSWER

3. What are the health consequences of high cholesterol?
   INSERT ANSWER

4. What could be causing Renee’s high cholesterol levels? Describe at least three possible contributing factors.
   INSERT ANSWER

Part II

Renee’s meeting with the doctor went well. He told her that although her cholesterol was currently high, it could be managed. However, the doctor was concerned that her high cholesterol could be familial hypercholesterolemia, a type of inherited disorder that leads to high cholesterol. After prescribing statins and counseling Renee on some lifestyle changes, the doctor referred Renee to a genetic counselor. Renee and Karl were both a mixture of relieved that the disease could be managed, and concerned that it might be genetic.

1. What are statins? How do they function?
   INSERT ANSWER

2. What is the inheritance pattern of familial hypercholesterolemia? Remember to cite your sources using APA Style.
   INSERT ANSWER
   
3. If Renee has familial hypercholesterolemia, what is/are her possible genotype(s)?
   INSERT ANSWER

4. Why might Renee and Karl be concerned that Renee’s hypercholesterolemia might be genetic?

INSERT ANSWER

Part III

Renee met with the genetic counselor, Guillermo. Guillermo explained that they would first construct a pedigree. He asked Renee to list all her blood family members back to her grandparents, and for each person mark whether he or she had had a myocardial infarction (i.e., heart attack) before 50 and/or high cholesterol.

1. Below is the information Renee listed. Use this to construct a pedigree. Any person with a heart attack before 50 and/or high cholesterol is considered affected.

Renee (self), High cholesterol

Sister, No history of either

Brother, High cholesterol

Father, Myocardial infarction at 45, died

Mother, No history of either

Maternal aunt, No history of either

Paternal uncle, High cholesterol

Paternal grandmother, High cholesterol and myocardial infarction at 49, 55, died

Paternal grandfather, No history of either

Maternal grandmother, No history of either

Maternal grandfather, High cholesterol

2. Based on the pedigree above and your knowledge of genetics, do you think Renee has an inherited form of hypercholesterolemia? Please support your answer.
   INSERT ANSWER
   
3. If not genetic, is there another explanation for the prevalence of myocardial infarctions and high cholesterol in this pedigree? Please explain.
   INSERT ANSWER

Part IV

Based on the pedigree, the genetic counselor thinks that Renee might have familial hypercholesterolemia. He explains that there is a genetic test for the most common form of the disorder, which is a mutation in the LDLR gene, or low-density lipoprotein receptor gene. This leads to a nonfunctional receptor and LDL not being removed from the blood, which causes high cholesterol. He briefly explains the risks and benefits of testing. “On the legal side, currently, health insurers cannot discriminate against you or charge you higher rates if you test positive. However, life insurers can. It might benefit you to sign up before testing if you do not already have coverage. This also has implications for your family members, including your children. As an autosomal dominant disorder…”

1. Complete the genetic counselor’s explanation of the effects the knowledge might have on Renee and Karl’s children. Include an explanation of autosomal dominant inheritance.
   INSERT ANSWER

2. Would you have the genetic test done? There is no right or wrong answer to this question, just a well-supported one. Please include at least one resource that you’ve found on the benefits and risks of genetic testing. Cite your source using APA Style.
   INSERT ANSWER

Part V

Renee decides to have the LDLR genetic test done. The results are positive for one copy of the mutated LDLR gene.

1. What is Renee’s genotype?
   INSERT ANSWER

2. What is Renee’s phenotype?
   INSERT ANSWER

3. What is the probability that either of her children has familial hypercholesterolemia?
   INSERT ANSWER

4. If Renee and Karl adopted a child, would that child be at increased risk for familial hypercholesterolemia based on Renee’s results? Please explain.
   INSERT ANSWER

Answer 1

The lipoprotein profile includes Total cholesterol. LDL(low-density lipoprotein cholesterol, also called "bad" cholesterol) and HDL (high-density lipoprotein cholesterol, also called "good" cholesterol).

Cholesterol is a major component of all cell membranes and is used to make essential molecules such as hormones, fat-soluble vitamins, and bile acids to help you digest your food. The body needs cholesterol but it can make its own – you don't need to consume cholesterol in your diet.

High cholesterol can cause a dangerous accumulation of cholesterol and other deposits on the walls of your arteries (atherosclerosis). These deposits (plaques) can reduce blood flow through your arteries, which can cause complications, such as: Chest pain and heart attack.

​Physical inactivity and a diet rich in saturated fats can lead to high cholesterol in Rene`s case. Also as her father passed away in the young age due to a heart attack so she may be at risk of the hereditary heart disease too. Thus the three contributing factors are- lack of physical activity, diet and heredity.

part II

Statins have been clearly shown to reduce blood cholesterol and prevent atherosclerosis, or heart disease. They work by reducing the liver's production of cholesterol. They block an enzyme called HMG CoA Reductase that the liver uses to make cholesterol.

Inherited forms of hypercholesterolemia result from autosomal dominance pattern. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder.

If Rene has hypercholesterolemia then it means her one copy of allele is defective i.e her genotype would be-Hh

They are worried as Rene`s father died of a heart attack at an early age.

Part III-

Yes as is evident from the pedigree analysis Rene could have inherited form of Hypercholesterolemia.

Part IV-

As an autosomal genetic disorder, their children might also suffer from it.

Dominant inheritance means an abnormal gene from one parent can cause disease. A parent with an autosomal dominant condition has a 50% chance of having a child with the condition. This is true for each pregnancy. It means that each child's risk for the disease does not depend on whether their sibling has the disease.

Yes, I would have done the test done so that I am well aware f my condition and what could be the chances of passing my genetic condition to my children.

Part V-

Rene`s genotype- Hh

Rene`s phenotype- having a high level of cholesterol

One gene is from the mother and one gene is from the father. A parent with an autosomal dominant disorder will pass on either a changed copy of the gene or a normal copy of a gene which is 50 -50. This means that there is a 50 - 50 probability of her children getting the disease.

The adopted child will not be at risk until we know his or her parent`s conditions.