Pathophysiology

Genetic Screening 

Cystic fibrosis (CF) is a genetic disorder primarily caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene encodes a protein that functions as an ion channel, and is crucial for regulating salt and water movement across cell membranes, particularly in epithelial cells such as those lining the lungs and digestive tract. Disrupting this regulation leads to decreased fluid secretion and altered epithelial surface hydration. Over 2,000 mutations in the CFTR gene have been identified. The most prevalent mutation is the deletion of phenylalanine at position 508 of the CFTR protein, known as F508del, which accounts for approximately 70% of CF cases. Other mutations can be homozygous (the same mutation on both alleles) or heterozygous (different mutations on each allele).

CF is an autosomal recessive disorder, meaning that an individual must inherit two mutated copies of the CFTR gene (one from each biological parent) to manifest the disease.

Exercise: Systemic Impact of Cystic Fibrosis and Screening

Fill in the blanks with the correct term: pancreas, intestines, liver, bile ducts, gallbladder, CFTR modulators, CFTR blockers, pulmonary, bladder, respiratory failure, reactive airway disease, diabetes, heart failure, all women, high-risk women

In the respiratory system, CF causes the mucus in the lungs to become thick and sticky, which clogs the airways and makes it difficult to breathe. This environment is conducive to bacterial growth, leading to frequent _____________ infections and chronic inflammation. Over time, these infections and the resulting inflammation can cause permanent damage, including bronchiectasis and _____________, which is the most common cause of death in CF patients. The thick mucus also affects the upper respiratory tract, leading to conditions such as chronic sinusitis, which can further obstruct airflow and cause additional complications. The persistent presence of mucus and bacteria in the airways results in a chronic cough, wheezing, and difficulty clearing the airway.

CF primarily affects the _____________ in the digestive system. The thick mucus blocks the ducts in the pancreas, preventing the release of digestive enzymes necessary for breaking down food. This leads to malabsorption of nutrients, particularly fats, proteins, and fat-soluble vitamins (A, D, E, and K), resulting in malnutrition and poor growth. The blockage can also cause pancreatic damage, leading to glucose intolerance and CF-related _____________. Additionally, CF can affect the _____________ by blocking the _____________, which can lead to liver disease, including cirrhosis. The intestines can also be impacted with intestinal blockages and conditions such as meconium ileus in newborns, which is a blockage caused by the baby’s first stool.

New treatment options have significantly improved outcomes for patients with CF. The development of a group of medications known as _____________ has been a breakthrough in CF treatment. They correct the defective CFTR protein, improving its function.

Prenatal and Newborn Screening 

The American College of Obstetricians and Gynecologists (ACOG) recommends that carrier screening for CF be offered to _____________ who are considering pregnancy or are currently pregnant. Patients are tested for the most common genetic mutations and any known CF-related genetic mutations that run in their family. In addition, all infants born in the United States are screened for CF soon after birth as part of newborn screening protocols. Carrier screening does not detect all possible CF-related genetic changes.  There are significant disparities and missed diagnoses with variants seen more commonly among infants of non-European descent. Efforts are being made in multiple states to expand their CF newborn screening panel to ensure that ethnicity-specific variants are not missed.

Case Study

Nurse Practitioner Lee is consulting with a couple, Sarah and Michael, who are expecting their first child. Sarah has a family history of CF and is known to be a carrier of the CF gene, which is autosomal recessive. Michael’s genotype for the CF gene is unknown, so NP Lee decides to order a genetic test. The test results show that Michael is also a carrier.

Using a Punnett square, NP Lee explains the likelihood of their child inheriting CF. The CF gene is represented by two alleles: ‘F’ for the normal allele and ‘f’ for the allele that causes CF. Since both Sarah and Michael are carriers, their genotypes are Ff.

F f
F FF F f
f f F f f

Punnett Square Interpretation

Match the correct interpretation to each possible genotype: Child does not have CF but is a carrier, Child does not have CF and is not a carrier, Child does have CF, Child not have CF but is a carrier.

F F : _______________________

f F : ________________________

F f : ________________________

f f : _________________________

Review Questions

Click the arrow to expand the section and view the correct answers.

  1. What is the probability that Sarah and Michael’s child will be a carrier of the CF gene?
    1. 25%
    2. 50%
    3. 75%
    4. 100%
Answer:

B) 50%
Feedback: There is a 50% chance that the child will inherit one normal allele and one CF allele, making them a carrier (Ff).

  1. If Sarah and Michael have four children, what is the expected number of children who will neither have CF nor be carriers?
    1. 1
    2. 2
    3. 3
    4. 4
Answer:

A) 1

Feedback: Statistically, 1 out of 4 children is expected to inherit two normal alleles (FF), which means they will neither have CF nor be carriers.

  1. Which genotype represents a child who has cystic fibrosis?
    1. FF
    2. Ff
    3. ff
    4. FFF
Answer:

C) ff

Feedback: The genotype ‘ff’ indicates that the child has inherited two alleles for CF, one from each parent, and will have the disease.

  1. What is the probability that Sarah and Michael’s child will have the disease?
    1. 25%
    2. 50%
    3. 75%
    4. 100%
Answer:

A) 25%

Feedback: There is a 25% chance that the child will inherit two CF alleles.

  1. Another pregnant patient has the genetic screening test done, and it is negative. The NP should now tell her:
    1. Your child does not have a risk of CF.
    2. You are not a carrier, so there’s no need to be concerned about the status of your partner.
    3. This is reassuring because CF screening covers the most common genetic variants; however, it does not include all variants of the disease.
    4. If the father has CF, the baby will have CF even if you are not a carrier.
Answer:

C) CF screening is reassuring, but it does not cover all variants of the disease.

Feedback: It is still important to explore the family history of both biological parents. Additional testing may be indicated if there is a family history, and newborn screening is still conducted.

References

The American College of Obstetricians and Gynecologists (ACOG). (2017). Carrier screening for genetic conditions. Committee Opinion No. 691. Obstetrics & Gynecology. 129, p. e41-e55. https://doi.org/10.1097/AOG.0000000000001952

Centers for Disease Control. (2024).  About Cystic Fibrosis.  Available at: https://www.cdc.gov/cystic-fibrosis/about/index.html

Microsoft. (2024). Copilot [AI assistant]. Microsoft Corporation.

Elborn, J. S. (2016). Cystic fibrosis. The Lancet, 388(10059), 2519-2531. https://doi.org/10.1016/S0140-6736(16)00576-6

Cystic Fibrosis Foundation. (n.d.). Lung health & CF. Retrieved February 22, 2025, from www.cff.org

Cystic Fibrosis Foundation. (n.d.). Digestive system & CF. Retrieved February 22, 2025, from www.cff.org

Cystic Fibrosis Foundation. (n.d.). Living with CF. Retrieved February 22, 2025, from www.cff.org

Heavey, E. (2024).  Lecture on genetics. [Transcript].

McGarry, M. E., Raraigh, K. S., Farrell, P., Shropshire, F., Padding, K., White, C., Dorley, M. C., Hicks, S., Ren, C. L., Tullis, K., Freedenberg, D., Wafford, Q. E., Hempstead, S. E., Taylor, M. A., Faro, A., Sontag, M. K., & McColley, S. A. (2025). Cystic fibrosis newborn screening: A systematic review-driven consensus guideline from the United States Cystic Fibrosis Foundation. International Journal of Neonatal Screening, 11(2), 24. https://doi.org/10.3390/ijns11020024

Tkacs, N. (Ed.). (2020). Advanced physiology and pathophysiology: Essentials for clinical practice. Springer Publishing Company.

You.com. (n.d.). Homepage. You.com. Retrieved February 22, 2025, from https://www.you.com

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Be Prepared for Your Nurse Practitioner Clinical Readiness Exam Copyright © 2026 by Elizabeth Heavey, Renee Biedlingmaier, Colleen Burgoyne and Carnel C. Jackson is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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