Introducing
Your new presentation assistant.
Refine, enhance, and tailor your content, source relevant images, and edit visuals quicker than ever before.
Trending searches
Ataxia Telangiectasia
Ataxia Telangiectasia/Louis-Bar Syndrome
General Information
What is Axatia Telangiectasia?
Ataxia telangiectasia is a rare inherited disorder that affects the nervous, immune, and other body systems. The disease derives from two parts: ataxia (loss of full control due to the deterioration of the nervous system) and telangiectasia (widening of blood vessels, like in the eyes).
General Information
Heredity
Heredity
Ataxia-Telangiectasia is an autosomal recessive disease, meaning that one can only inherit the disease if both parents are carriers of an ATM mutation.
- Carriers, although they do not have the disease, often have higher chances of developing cancer due to a weakened immune system
- 1% of people have one regular and one mutated gene
On average, 1 in 40,000-100,000 people will have Ataxia-Telangiectasia. Children who have parents who are carriers of the mutation have a 1/4 chance of inheriting the disease.
Children who have carrier parents:
- 1/4 chance of having ataxia telangiectasia
- 1/2 chance of being a carrier
- 1/4 chance of being free from the disease
Background on ATM
The mutation occurs on the ATM gene, located on chromosome 11. ATM's main purpose is to provide instructions for producing a protein/proteins that controls cell division and repair. It is part of the PIKK (phosphatidylinositol 3-kinase related kinase) family, essentially a serine/threonine specific kinase, and is an inactive dimer until activated in response to double stranded breaks or oxidative stress.
Mutation
Chromosome 11
ATM is a DNA damage checkpoint!
Mutation Diagram
Normal Cell vs.
Mutated Cell
Mutation of ATM
With a normal ATM gene, it checks the DNA during the G2 phase of the cell cycle in order to find broken DNA. Essentially, it is at a checkpoint in the cell cycle where the ATM double checks and repairs DNA before it duplicates.
However, those with an ATM mutation often lack the ability for their ATM to check on the DNA, causing broken DNA to replicate. As a result, those with ataxia-telangiectasia are at a much higher rate of developing cancer due to the replication of damaged/unrepaired DNA.
Mutation of ATM
Case Study
Discovery of the ATM mutation in ataxia telangiectasia was only recently found in 1995 by Yosef Shiloh and his team of international scientists. By pinpointing where they believed the ATM gene was located (chromosome 11) and searching in the chromosome, they found out that ataxia telangiectasia patients often had a mutation or lack of ATM, which allowed them to become one step closer to unraveling the mysterious disease.
Evidence
Taken from the Shiloh Laboratory website.
Bloodshot eyes
Symptoms
Poor Coughing
Symptoms
- Difficulty in coordination movements before age 5
- Difficulty walking, issues with overall balance, jerking/tremors due to muscle contradictions
- Result: many are placed in wheelchairs at a young age
- Disturbance in nerve function
- Slurred speech
- Lack of muscle coordination leads to poor coughing, issues with breathing and swallowing
- Oculomotor apraxia (trouble with moving eyes)
-Telangiectasias: enlarged blood vessels around eyes, eyes seem “bloodshot”
- Much higher chances of developing cancers, specifically blood/immune system cancers
-leukemia, lymphoma
Difficulty walking
Type of Cell Communication
Ataxia-telangiectasia uses tyrosine kinase receptors, which are specialized in regulating the cell cycle and the growth of the cell. Tyrosine kinase receptors use dimers, such as ATM (an inactive dimer) in order to fully activate and phosphorylate. ATM is activated through the signaling of broken DNA, in which goes through numerous pathways, such as allowing proteins like NBS1 (nibrin) to relocate themselves to DSBs (double stranded break) and repair the DNA or apoptosis, if necessary.
Cell Communication
Faulty Communication Pathway
Faulty Communication Pathway
The mutation of the ATM gene, which can be caused by hundreds of mutations leading to an inactive, non-functioning kinase, is one of the main reasons why ataxia-telangiectasia occurs. Since the ATM gene helps repair and fix DNA, a mutated version causes broken DNA to continue replicating and spreads throughout the body to other genes. As a result, cancers and tumors can easily form with the broken DNA. Cells can also incorrectly die, which is why people with ataxia telangiectasia often have difficulty with coordination, as the brain cells necessary to complete the process are killed off/go through apoptosis.
What is the correct pathway?
Properly Working Pathway
ATM is crucial in the cell cycle and maintenance of the cell. This diagram shows ATM functioning correctly in the various transduction pathways as it begins to activate other kinase that each serve a purpose in checking and repairing DNA.
Diagram
Note: ATM is in green.
Work Cited
References
ATM gene - Genetics Home Reference - NIH. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/ATM#conditions
Ambrose, M., & Gatti, R. A. (2013, May 16). Pathogenesis of ataxia-telangiectasia: The next generation of ATM functions. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709651/
Ataxia Telangiectasia. (n.d.). Retrieved from https://rarediseases.org/rare-diseases/ataxia-telangiectasia/
Awasthi, P., Foiani, M., & Kumar, A. (2015, December 01). ATM and ATR signaling at a glance. Retrieved from https://jcs.biologists.org/content/128/23/4255
Gene Found for Fatal Childhood Disease, Ataxia-Telangiectasia. (n.d.). Retrieved from https://www.genome.gov/10000522/1995-release-ataxiatelangiectasia-gene
Mahajan, K., & Mahajan, N. P. (2015, December 15). Cross talk of tyrosine kinases with the DNA damage signaling pathways. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678820/
Momčilović, O., Choi, S., Varum, S., Bakkenist, C., Schatten, G., & Navara, C. (2009, May 14). Ionizing Radiation Induces Ataxia Telangiectasia Mutated‐Dependent Checkpoint Signaling and G2 But Not G1 Cell Cycle Arrest in Pluripotent Human Embryonic Stem Cells. Retrieved from https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.123
The Shiloh Laboratory: Yossi Shiloh: Sackler School of Medicine: Tel Aviv University. (n.d.). Retrieved from https://m.tau.ac.il/~yossih/index.htm
Teive, H. A., Moro, A., Moscovich, M., Arruda, W. O., Munhoz, R. P., Raskin, S., & Ashizawa, T. (2015, August 15). Ataxia-telangiectasia - A historical review and a proposal for a new designation: ATM syndrome. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161405/
What is Ataxia? (n.d.). Retrieved from https://ataxia.org/what-is-ataxia/