Wednesday, June 28, 2017

Project Lead the Way (PLTW) Biomedical Science and Questions

Sometime last school year Becca applied to the biomedical program at Franklin High School and got accepted. She was super excited. 

This program allows students to explore the concepts of human medicine through an introduction of topics such as physiology, genetics, microbiology and public health. Students acquire strong teamwork and communication practices, and develop organizational, critical-thinking, and problem-solving skills as they investigate various health conditions and infectious diseases, examine the interactions of human body systems, and explore how to prevent and fight infection. In Grade 12, students have the opportunity to work on an independent project with a mentor. Successful completion of the program allows students to pursue post-secondary education and careers in the biomedical sciences.

Program of Study
Grade 9 - Principles of the Biomedical Sciences
Grade 10 - Human Body Systems
Grade 11 - Medical Interventions
Grade 12 - Biomedical Innovation PLTWW Biomed CWE

A few weeks ago, she spent 3 1/2 days at the high school for a biomedical camp. The point of the camp was for the kids to meet others in the program, get a feel for the school as well as a feel for the program. Each day was a different topic. Becca loved each day and came home excited about each topic. One of the days was genetics, this led to some questions on her part, I did the best i could to answer them as well as let her read the report from Ian's initial diagnosis in 2012. This answered some of her questions but also led to more questions. With those I reached out to the genetic counselor we used in 2012 with her questions. Here is the wonderful letter she wrote back to Becca. 

Dear Becca,

I hope you are doing okay given all you have been through with losing Ian.  He was a special boy and is remembered by so many people, as I am sure you know.  I don’t know if you remember me, but I worked with Dr. Raymond at Kennedy Krieger and was one of the people who helped to figure out what was causing Ian’s problems.  

Your mom tells me that you’re studying genetics in school now and that you have some questions about the genetic cause of Ian’s condition.  Genetics is a huge topic and there is lots to learn, but I have tried to cover some basics in this message as a starting point.

By now you have probably learned about chromosomes, genes, and DNA.  DNA is a chemical substance contained in each of our cells and it is made up of four chemical units that we call “nucleotides”.  They each have specific names.  We abbreviate the names using the letters A, G, T, and C.  We have more than 3 billion of these DNA letters in our genome, but they are soo microscopically tiny that we cannot see them with the naked eye.  We have two copies of all of our genetic information.  One set comes from our mother (the egg) and one set comes from our father (the sperm).   So we have double of everything, which is designed to give us a backup system in case a gene is broken or not working. 

Clusters of DNA letters form genes, and we give these genes names depending on what they do.  Most genes contain instructions that tell our bodies to make important proteins or other molecules that our bodies need in order to function.  Some genes are responsible for making enzymes that digest the food in our stomachs.  Other genes are responsible for protecting us from damaging UV rays that can cause cancer.  Some genes make up the cells that allow our brains to retrieve memories.  There are probably about 25,000 genes in total and some of them are responsible for doing more than one thing.   Some genetic conditions are caused by mistakes, or disruptions, in genes that play very important roles in our bodies.  This is the type of genetic problem Ian had (more about this below).   Sometimes people call these mistakes “mutations” - that is not a word that I love, but you will hear people use it.

The genes are strung together a bit like necklaces and they are wrapped around structures in our cells called chromosomes.  The chromosomes are the little worm-like things you see inside cells and we have 46 in total (23 from mom, 23 from dad).  Again, double of everything.  The final pair of chromosomes are called “sex” chromosomes.  Men have one X chromosome and one Y chromosome (the Y chromosome is tiny!) and women have two X chromosomes.  Genes on the Y chromosome are what cause men to develop some different features than women.   Some genetic conditions are caused by deletions, breakages, or duplications of chromosome material, in which whole clusters of genes are either missing or duplicated or disrupted.  You might learn about a condition called Down syndrome.  People with Down syndrome have a whole extra copy of chromosome 21, which is a LOT of extra genetic material, so they can have a lot of health issues.   Sometimes if babies have deleted or duplicated chromosomes they are too sick to ever make it out of the womb, and this is how a lot of pregnancy miscarriages are caused.  Ian did not have a chromosome disorder.

The gene that was affected in Ian’s case is called VRK1 and it is located on chromosome 14.  When Ian was diagnosed, we did not know very much about what this gene does, and today we still don’t have a lot of information about it.   Recent research shows that VRK1 is an important gene for the development and regulation of the central nervous system (the spinal cord and the brain) and that brain and nervous system structures cannot develop or sustain themselves without it.   Your mom and dad each carry one broken copy of this gene and one working copy of this gene (not their fault!  These things happen randomly).  You also carry one broken copy and one working copy.  The good news for the three of you is that one working copy is enough to keep you healthy and functioning normally.   However, unfortunately, Ian inherited the broken copy from both your mom and your dad, so he had two broken copies and this is why he was sick.   

Conditions that require two broken copies in order to happen are called autosomal recessive conditions.   You will also learn about dominant conditions which only require one broken copy of a gene, and you will learn about X-linked conditions caused by genes on the X chromosome.   These are each inherited in families in different ways.   Autosomal recessive conditions are usually very rare, but sometimes they run more commonly in populations that have a lot of shared ancestry, like Ashkenazi Jewish people.  We think that the mutation in your family may be more common in families of Ashkenazi Jewish descent.

The specific VRK1 mutation in your family is called c.C1072T; p.R358X.  What this means is that a “C” in position 1072 in the VRK1 gene was changed to a “T”.  This change in the code meant that instead of making a full VRK1 protein, Ian’s body stopped making the protein altogether.  We call this a “nonsense” mutation because the DNA code stops making sense and thus the body stops making the protein it’s supposed to be making.  Since both copies of the VRK1 gene were affected in Ian, his body did not have this protein at all and that is why we think he developed differently.

It is important to remember that we are more than just our genes.  Two children with Down syndrome, or two children with VRK1 mutations, will still be very different from one another and there are many other things that affect our health and how we grow and develop, such as our environment and our different combinations of other genes.  But some genes have very important functions and when we see mistakes in these genes they can have serious consequences for health.

We do not expect you to ever have any problems like Ian, because your fully working VRK1 gene is doing the job you need it to do.  However, when you decide to have children of your own, it will be important for your partner to have testing to see if he carries any mutation in the VRK1 gene, especially if he is also Jewish.   There are other genetic diseases that run more commonly in Jewish families, such as Tay-Sachs disease, so it will be important for you and him to have carrier testing for these conditions as well.

Here are some links with visuals corresponding to the concepts discussed above.  I hope this answers some of your questions and isn’t too basic or too complicated.  Please feel free to get in touch if anything is unclear.

All the best,

I'm sure over time more questions will come up and we will do our best to answer them as well as help her to continue to deal with her grief. She is doing ok after this weekend but the unveiling brought emotions to the for front for all of us. We continue our grief therapy as well as private therapy to deal with the loss of Ian and the impact it has had on our lives individually as well as a family. As always, thank you to all who have been there for us over the years, especially this pass one as we have our year of firsts. 

1 comment:

Marci Scher said...

Carye George Everett Beautiful prayers for a wonderful boy who touched so many lives.