Part 1: Mutation Story

How are you as a gene affected?

Hi there, I’m the ASPA gene, or the aspartoacylase gene. I’m located in the P arm of chromosome 17, section 13.2 in Lenny’s DNA.  My normal purpose is to provide instructions for the production of an important enzyme called aspartoacylase. Aspartoacylase is an enzyme that breaks down a compound called NNA in the brain’s neurons, the NNA (or N-acetyl-L-aspartic acid) is converted into aspartic acid, which is an amino acid that is building block for several proteins, as well as an acid called acetic acid. But there is something different about Lenny’s ASPA gene, I do not function like I am supposed to. Lenny is the host of Canavan Disease, a disease caused by different mutations in me, the ASPA gene. For Lenny, the cause of Canavan Disease is the partial deletion of me, the ASPA gene, that leaves Lenny with the inability to produce aspartoacylase.

What caused your mutation?

Lenny’s Canavan Disease is passed on to him by his parents, who are both carriers of Canavan Disease, although they are not affected. The ASPA gene mutation is recessive and has to be carried by both of Lenny’s parents in order for Lenny to have a chance in being affected. Lenny’s parents are most likely from German/Eastern European decent, because that is where the allele originated from, Lenny is 1 of 6,400-13,500 people from his decent to get Canavan Disease.  Lenny has 4 siblings, who have all been tested for Canavan Disease, Lenny is the unlucky 1/4 that is affected (rr allele), his two brothers are the 2/4 who are carriers (Rr allele), and his sister is the luckier 1/4 who is free from the mutation (RR allele). Canavan Disease can be caused from different mutations of the ASPA gene, but Lenny’s is the partial deletion if the gene (the only confirmed cause at this time). Much research still needs to be done to further our understanding of Canavan Disease.

How is the host/ host’s body affected? How is their daily life?

Canavan Disease is a type of disease called a Leukodystrophie, this means that Canavan Disease affects Lenny’s myelin sheath, the myelin sheath is a cover that protects nerves and helps transfer signals in the brain. Lenny was born a small baby, with an abnormally large head, and big blue eyes. Lenny’s first few months of life were normal, but after 5 months, his parent’s noticed Lenny having difficulties eating, sleeping and crawling, Lenny even had an epileptic seizure. Lenny’s visit to the doctor didn’t bring much good news either, as Lenny had Canavan Disease. After the first year of life, Lenny was struck with even more problems, Lenny was losing much of his motor ability, he could barely crawl, walk, or even sit, with a moderate form of paralysis. Lenny’s nerves were deteriorating, because there was a buildup of  N-acetyl-L-aspartic acid in his nerves, and Lenny could’t break it down into aspartic acid, an acid that helps build crucial proteins, without this acid, Lenny’s myelin sheath was disappearing, weakening Lenny’s motion signals and drastically decreasing Lenny’s control and strength of his muscles. Seizures became much more common for Lenny too, and his responses were delayed. Lenny had an very weak muscle tone, with his muscles becoming too soft or too stiff. Nowadays, Lenny has to be hooked up to an oxygen tank and monitored all day, Lenny has lost almost all voluntary muscle movement and sits in his wheelchair, waiting with his family for a cure expected to come in 3 years. Lenny’s parents are hoping for a medicine (lithium citrate) that decreases the amount of N-acetyl-L-aspartic acid in Lenny’s nerves to a normal level, for now, Lenny doesn’t visit the doctor very much because, the only treatment Lenny gets is for the separate symptoms. Lenny is six, and the life expectancy for a Canavan Diseased child is only ten years, but all he can do is wait and hope.

Part 2: The Making of the Story

Ask: I researched many questions to put together my story, some questions had very vague answers, and it was hard to find an exact answer.

1. What is Canavan Disease?
2. What are the symptoms of Canavan Disease?
3. What is the treatment for Canavan Disease?
4. Where did Canavan Disease originate?
5. What major affects does Canavan Disease have?
6. How is Canavan Disease inherited?
7. What are the chances of Inheriting Canavan disease? carrying it?
8.  What chromosome does Canavan Disease affect? what gene?
9. What is the purpose of the ASPA gene?
10. What requirements do people with Canavan Disease have?

Acquire: I got all of my information from sources Like the official disease’s page, a couple .gov pages (US Library of Medicine) and a couple YouTube videos, for specific facts that I didn’t find in articles.

Analyse: I checked over each website I used to make sure all the information agreed with other sites. Here is a list of the sources I used:

http://www.canavanfoundation.org/about_canavan_disease – answers question 1, 3, 4.

https://ghr.nlm.nih.gov/condition/canavan-disease# – answers question 5, 6, 7, 8, 9.

https://www.youtube.com/watch?v=tCB51efv5XE – answers question 2.

https://www.youtube.com/watch?v=UJXeAlAYiLI – answers question 10.

The rest of the sites build off of the questions:

http://www.ninds.nih.gov/disorders/canavan/canavan.htm

http://jmg.bmj.com/content/38/3/e9.full

https://philippat2014.wordpress.com/2015/11/09/canavan-disease/

Picture sources (respective order):

https://ghr.nlm.nih.gov/gene/ASPA#location

https://en.wikipedia.org/wiki/Canavan_disease#/media/File:Autorecessive.svg

https://philippat2014.wordpress.com/2015/11/09/canavan-disease/

Asses: Overall, I like my presentation and how I applied the information I learned. One of the struggles I had was finding information about the affected gene, Canavan Disease is still being researched and I found it hard to locate all the information I needed on one webpage. I think I did well on the information provided with the story, one way I could’ve enhanced my presentation is with an embedded video to reinforce my statements on the life of a child with Canavan syndrome. I enjoyed this project and learned about the 5 A’s and how to apply them in my future work.