Case Study: Stephanie Needs Your Help
Stephanie is a 47-year-old, mother of three living in the US. She lives an active lifestyle, frequently going on hikes
with her dog and to spin classes three to five times a week. However, she lately has been experiencing cramping in both of her calves while walking. At first attributing this to simply overworking herself, she then noticed that she was tiring quicker and experiencing shortness of breath. She then became especially concerned when she noticed some extremely small, yellow bumps on her Achilles tendons (located directly behind her ankle) and went to see a doctor. Her doctor ordered some blood tests that had telling results:
- Total Cholesterol: 350 mg/dL (high)
- Normal Total Cholesterol Levels: Less than 200 mg/dL
- LDL-C: 270 mg/dL (very high)
- Normal LDL-C Levels: Less than 129 mg/dL
- Triglyceride Levels: Normal
Stephanie’s doctor further questioned her on her family history. Stephanie’s father died at the young age of 42 from a heart attack, and both of her paternal grandparents died from heart attacks as well. Stephanie’s older brother, Leonard, has had no major health problems, but her older sister, Crystal, has been on Lovastatin for a few years now. Based off of Stephanie’s results and family history, her doctor was able to make a diagnosis and prescribed Stephanie Pravastatin and suggested that she continues to exercise regularly and regulate her intake of beef, chicken, pork, lamb, and full-fat dairy products.
What is Stephanie’s diagnosis?
Stephanie was diagnosed with familial hypercholesterolemia (FH), which causes severe elevations of total cholesterol and low-density lipoprotein cholesterol. The disease is inherited genetically. Based upon the pedigree of Stephanie’s family, can you answer the following questions. Don’t know how to read a pedigree? Learn how here.
The disease’s inheritance pattern is autosomal dominant, meaning that an individual will have the condition with just one copy of the defective gene. Someone who inherits a single copy of the mutated gene will have what is called heterozygous familial hypercholesterolemia (or HeFH). One would have homozygous familial hypercholesterolemia (or HoFH) if both copies of the defective gene are inherited– one from each parent. Want to learn more about the genetics of FH? Check out this link HERE.
There is no cure for FH, and treatment only helps with reducing the risk of heart disease. It requires daily medication (discussed above in the case study), and a special procedure called apheresis in the most severe cases.
Though this is mainly a “Call to Action” project, I did want to raise awareness for FH. As such, I’ve created a website that goes into more depth about what exactly FH is, learn more about how cholesterol impacts the body (both in those with and without FH), learn more about the genetics of FH, and ways that you can get involved around the world. Check it out HERE.
Are you at risk for FH? Take this quiz and find out!
What is Genome Editing?
At a young age, we learn that our DNA is what makes us unique– that our unique sequence within our genes is what makes us, us. However, our DNA is not perfect and there are mutations in our genes that cause a wide variety of disorders such as cystic fibrosis or Huntington’s disease. Recent advancements have allowed for the development of relatively cheap and fast DNA sequencing tools which have revolutionized our understanding of genetic diseases. By editing the genome, we can treat many inherited genetic diseases.
This proposed treatment is different than gene therapy (which involves the insertion of a new gene into cells to combat a mutated gene). Genome editing attacks the mutated gene directly, and explicitly alters the DNA.
What Is It?
CRISPR (clustered regularly interspaced short palindromic repeats) is a tool that can target nearly any genomic location and potentially repair broken genes by removing, adding, or editing different sections of the DNA sequence. It employs the use of a protein-RNA complex (Cas9) which will bind to a guide RNA (gRNA) molecule that is engineered to recognize a specific sequence. Today, CRISPR is the most versatile and precise method of genome editing.
How Does It Work?
Does it always work?
One current issue with CRISPR-Cas9 is that it doesn’t always work. The guide RNA doesn’t always lead the Cas9 protein to the right location. This is because the DNA code is so redundant, and so the gRNA sometimes goes to a different sequence that is nearly identical. The effects of this can range from no effect to cell death. While this is clearly problematic, there have been significant efforts made to reduce this issue.
Genome Editing and Curing FH
FH is caused by a mutation on Chromosome 19. If we could harness the CRISPR-Cas9 technologies, then we would be able to alter one’s genome and fix this mutation. Many companies are already using this technology to treat diseases. The following are a handful!
The biggest ethical consideration is the use of this technology for non-medical purposes. Many people would agree that editing the genome to cure awful diseases is morally acceptable. However, if we can cure diseases, can we also edit the genome to say, make someone an amazing athlete? Can we edit the genome for cosmetic purposes– altering eye color, hair color, and height? People dye their hair anyway, and wear contacts to change their eye color– so would it really be that bad to alter the genome for these purposes? To what extent can humans interfere with nature? What are the societal consequences of genome editing? Will this technology only benefit the wealthy? Just because we have this technology, does it mean that we should use it?