Overview
Cystic Fibrosis Genetic Variants W1282X
This project is going to be a report where you will be taking the role of a genetic counselor to the parents of a one-year-old child who has been diagnosed with Cystic Fibrosis W1282X. You will be presenting information about a particular variant (mutation) or pair of variants that cause Cystic Fibrosis. You will investigatea variant that you will be assigned, both on its own with an unknown variant on the other chromosome, or with a known common CF variant.
There are a variety of web sites that have specific information about cystic fibrosis as a disease and descriptions of the etiology of the disease. The most common websites with reliable information include the following:
https://investors.vrtx.com/news-releases/news-release-details/fda-approves-symdekor-tezacaftorivacaftor-and-ivacaftor-treat
You should read through each of these web sites and become familiar with the information contained in each one. Information in them will help form the basis of some of the background information for your report. You already know a lot of the basic information from class so these sites should help review what you know or add additional information to what you already know.
We have reviewed in this course how there are six classes of variants to which the most common CF variants can be assigned, classes I through VI (Note: there are a few websites that will show 5 different CF mutation classes; these have older information and are missing the 6th variant description). Information on the manner in which variants in each of these classes causes damage to the CFTR protein can be found at the following websites:
https://hopkinscf.org/knowledge/cftr/#section5
https://www.cff.org/What-is-CF/Genetics/Types-of-CFTR-Mutations/
This website shows only 5 classes of mutations, but the graphic presented is very helpful for understanding the mutation types. The first 5 classes of mutations are the same in each case; the 6thclass is a newer variant that is not described everywhere.
Investigating your Variant
Now that you have investigated some basic information about Cystic Fibrosis, the remainder of the project will present information that is specific to the variant that you areinvestigating. You will find the name of the variant that you have been assigned on the sheet labeled Student Assignments Gene Variants FA2023. The variant that you have been assigned will form the basis of your report. Your report must be no more than 5 pages (single sided), double spaced in a 12 point font with 1 inch margins. You may include charts/tables to summarize information and make it easier to follow.
What variant class does your specific variant belong to?
Use the previous information you have researched to determine which class your variant belongs to. You should describe the specific molecular problem with your variant in your report and how this problem results in a problem causing Cystic Fibrosis.
Next, go to the website at https://cftr2.org/
The entry page to this website will require you to read through and answer some questions in order to get to the actual database site where you can investigate your mutation. Once you have done this, it will take you to the main page where you will see the following:
Database Entry Point: This is the place where you will enter the names of the variant(s) that you are researching
Site Use Tips: This section describes the type of information found in the database. Ignore the first short paragraph about the videos, read the remainder of this section and then and see the next section on Instructional Videos.
Once you have done that, you can enter data in the entry points at the top left of the page ( https://cftr2.org/welcome ); there are two entry points; the first says Enter first variant and the second says Second variant (optional).
If you want to find information about a single variant, you should enter the name of the variant in the left box at the data entry point. Click on “submit” and you will come to the next page which summarizes information about the variant. Below the data entry box, this page will also give you an option to switch to another page which is the “healthcare/science” view. There is more detailed information in this view, much of which you will probably not understand. However, if you go through the information in this view, you may find a few pieces of information that will support your project. For example, in some cases, you can find information on the specific type of mutation (for example, a deletion variant) that is the cause of the variant. You can toggle back and forth between the general view and the healthcare/science view by clicking on the link.
The goal for this project is for you to research three possible situations:
1. Your assigned variant alone; since a person must have two of the genes for cystic fibrosis in order to have the disease, this search will give you information about a situation where a person has cystic fibrosis, but only one of the variants has been identified and the second is unknown.
2. Your assigned variant in both positions (this means that the same variant has been determined to be present on both chromosomes)
3. Your assigned variant in combination with variant F508del in the second position.
Each of these combinations will need to be run separately in the database and different information may be examined for each combination. You should report on each of these situations in your report. Each time you run a combination, you will be given results that you should include in your report including
1) Summary Information
2) Lung Function
3) % with Pancreatic Insufficiency
4) Pseudomonas Infection rate
The most efficient way to present this information is in a table that addresses each of the three situations. You can add additional pieces of information to the table to make the report efficient (for example, #5 below).
Report Layout: As you write your report, you should includethe following:
1) General information about cystic fibrosis as a disease; assume you are describing this information to the child’s parents who do not have a science background.
2) general background about your specific CF mutation and the class it falls into, including the molecular errors that result from the mutation.
3) the information you have researched about your specific variant and the implications of the different allele combinations that you researched.
4) What are the most common clinical manifestations for this variant?
5) What percentage of the population with CF carry this variant?
6) Is it possible to screen people for the presence of this variant?
7) What treatments may be available for treatment of this patient? Include traditional types of treatments and any newer CFTR modulator treatments and how they work with this variant. Information about treatments available with some of the new drugs can be found in the information below. The “healthcare/science” view in the database will give you some information about which (if any) of the new types of modulator drugs are effective for this mutation.
The following web sites contain information about testing that can be done to identify the CFTR variants in humans.
https://www.acog.org/Patients/FAQs/Cystic-Fibrosis...
https://ltd.aruplab.com/Tests/Pdf/182
https://www.labcorp.com/test-menu/23686/cystic-fib...
Possible Treatments
There are many old style standard therapies to treat CF, and there are the newer CFTR Modulator treatments. Which of these treatments might be useful for patients with your gene variant? As you do your database search, there will usually be some information that comes up about whether any of the newer modulator treatments is possible. There are other web sites where you can find specific information if you google the specific name of one of the new modulator treatments. Otherwise you should look into some of the older, standard treatments for the disease.
https://www.vertextreatments.com/