1. Progeria Tom Rafanan & Sarah Mumbert Ms. Henriques: Honors Biology P5 3 April 2015 www.google.com/imghp

2. What is Progeria? Progeria, or Hutchinson-Gilford Progeria Syndrome (HGPS), is an extremely rare genetic disorder of unknown origin that causes children to age prematurely and rapidly (8-10 times faster than the average child). It affects many parts of the body, including skin, bones, and arteries, starting in the beginning two years of life www.google.com/imghp

3. What Are the Symptoms? Usually within the first year of life, the growth of a child with progeria slows significantly, while their mental capacity and intelligence remains average (sometimes even above average)

4. o Below average height and weight (< 3.7 feet and 40 pounds) o Narrowed face, small lower jaw, thin lips, narrow nose o Head disproportionately large for face o Prominent eyes o Hair loss (including eyelashes and eyebrows) o Wrinkled skin o High-pitched voice o Visible veins o Abnormal tooth formations o Loss of muscle mass o Fragile bones and nails o Severe cardiovascular disease o No impairment on mental capacity www.google.com/imghp

6. Is it a Genetic Mutation, or what?

7. Progeria is a Gene Mutation o Affects autosomal chromosome 1 o ‘Normal’ karyotype since it is a point mutation www.google.com/imghp

8. o Mutation is on long arm (q) at point 22. It is denoted as “1q22.”

9. What is the Actual Disorder? o Mutation in LMNA gene o LMNA gene provides instruction for making proteins called lamin A, a protein that plays an important role in determining shape of nuclei in cells o The lamin A is defective and makes unstable nucleus—lead process in mature aging. o Once lamin A protein is mutated, it is referred to as Progerin www.google.com/imghp

10. Lamin A Proteins Affecting Cell Nuclei www.google.com/imghp

11. How is Progeria Passed On? o “Sporadic (random) autosomal dominant” mutation o NOT HEREDITARY o Most patients die before getting the chance to reproduce o Patients do not hit puberty or develop sex hormones www.google.com/imghp

12. So, How Does Someone Get Progeria? o Everyone makes a little bit of the protein Progerin; it is not as concentrated as it is in Progeria patients, however. o If you are born with Progeria, the amount of Progerin proteins in your cells is larger than usual. o In those who are not diagnosed, the small amounts of Progerin build up over a lifetime, possibly responsible for aspects of aging.

13. www.google.com/imghp

14. Who Does Progeria Affect? o All races and both sexes are affected equally, although it is common in Caucasians o There is an estimated 200-250 children with Progeria worldwide at any one time o Reported in 40+ countries (even one reported case in Hawaii) www.google.com/imghp

15. What Are My Odds? o Parents who have not had a child with Progeria have a 1 in 4-8 million chance of having a newborn with the disease o For parents who have already had a child with Progeria, the chances of it happening again is much higher at about 2-3%. o This is due to a condition called “mosaicism,” where a parent has the genetic mutation for Progeria in a small portion of their cells, but does not have Progeria. www.google.com/imghp

16. Lifespan and Possible Cures

17. How Long Do Patients Typically Live? o About 13 years old o Average life span ranges from 7 to 17 years old o Progeria makes patients more susceptible to premature heart diseases, so eventual death is mainly caused by heart problems (enlarged heart), strokes, hypertension (high blood pressure), and other cardiovascular diseases. www.google.com/imghp

18. Is There a Cure? No cure is definitely known at this moment.

19. But These Things Do Help o Psychological support (wigs) o Nitroglycerin (permits blood flow and relaxes muscle fibers) o Aspirin (regulate heart patterns) o High calorie dietary supplements www.google.com/imghp

20. Research on Progeria Itself o In September 2012, scientists discovered a possible cure for HPS: ‘farnesyltransferase inhibitor’ (or FTI for short) o Farnesyltransferase is an enzyme that plays a role in the development of progeria and cancer. o FTI drugs prevent certain cancer/progeria-causing proteins that require farnesyltransferase for function; FTI drugs are capable of reversing the dramatic nuclear structure abnormalities o Subjects tested with the drug showed improvement www.google.com/imghp

21. Progeria Research Foundation helps! It funds medical research aimed at developing treatments and a cure for Progeria www.google.com/imghp

22. Progeria Research Foundation (PRF) o Founded in 1999 o In April 2010, PRF published The Progeria Handbook for families and doctors o It created the Diagnostic Testing Program to test a patient’s blood and identify if s/he has progeria www.google.com/imghp

23. Ashley Hegi https://www.youtube.com/watch?v=8D4S3pDjPiU

24. https://www.youtube.com/watch?v=Fekab9Pu2us&spfreload=10 Remembering Sam Berns

25. Works Cited o "About Progeria." Progeria Research Foundation. N.p., n.d. Web. 03 Apr. 2015. o "Hutchinson-Gilford Progeria Syndrome." Genetics Home Reference. N.p., 30 Mar. 2015. Web. 02 Apr. 2015. o "LMNA Gene." Genetics Home Reference. N.p., n.d. Web. 03 Apr. 2015. o Narins, Brigham. "Progeria Syndrome." The Gale Encyclopedia of Genetic Disorders. 2nd ed. Vol. 2. Farmington Hills, MI: Thomson/Gale, 2005. 1063-065. Print. o "Progeria." Definition. Mayo Clinic Staff, 3 May 2014. Web. 02 Apr. 2015.