Progeria Tom Rafanan & Sarah Mumbert Ms. Henriques: Honors Biology P5 3 April

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

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)

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

Is it a Genetic Mutation, or what?

Progeria is a Gene Mutation o Affects autosomal chromosome 1 o ‘Normal’ karyotype since it is a point mutation

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

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

Lamin A Proteins Affecting Cell Nuclei

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

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.

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

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.

Lifespan and Possible Cures

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.

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

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

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

Progeria Research Foundation helps! It funds medical research aimed at developing treatments and a cure for Progeria

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

Ashley Hegi

Remembering Sam Berns

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