Kaylas Paper

Progeria Syndrome

It is every mothers dream to give birth to a healthy baby that they can take care of and watch grow and live until they get old, but what if you found out that your baby was born without any complications then during the first year of life they developed Progeria Syndrome and were told they were only going to live until age 12. In this paper I am going to explain genetically what causes Progeria, what it does to the body, some treatments going on right now, and some case studies about Progeria.
Progeria is also known as Hutchinson-Gilford progeria syndrome because of Dr. Jonathan Hutchinson who first described this syndrome in 1886, and then Dr. Hastings Gilford who also described it in 1904. Even though these two researchers described Progeria a long time ago, there wasn’t any real research on a cure until the 1900’s. This syndrome is known as the premature aging disease. As being researched, researchers have found that the cause of Progeria is from a mutant lamin A protein. The Importance of Lamin A is that it is a structural protein called intermediate filament proteins. Intermediate filaments provide stability and strength to cells. Lamins A proteins are essential scaffolding components of the nuclear envelope, which is a structure that surrounds the nucleus in cells. (McClintock 2006) In normal cells, prelamin A is a “CAAX protein” that is processed and generated to mature lamin A, which is a structural protein of the nuclear lamina allowing a stabilization of the inner membrane of a cell’s nucleus. (Yang 2005) In a progeria mutant cell, the nucleus’s in the cell are detached and abnormally shaped, thickened nuclear lamina, cluster of nuclear pores, and loss of heterochromatin. Heterochromatin is a tightly packed form of DNA. Its major characteristic is that transcription is limited. As such, it is a means to control gene expression, through regulation of the transcription initiation. They also are protein lacking 50 aa near the C terminus. (Goldman 2004) The lamina is important because they are distributed throughout the nucleoplasm and are vital for DNA replication and RNA polymerase II transcription. (Shumaker 2006)
As a result to the mutant cells, children age much faster then their bodies can handle. Children will look normal when they are born, but during the first year of growth symptoms will start to develop. These symptoms are growth rate slows down they are much shorter and weight a lot less for their age, baldness, aged-looking skin, a pinched nose, small face and jaw, and a big head. Many children will also develop progressive cardiovascular disease. Many develop atherosclerosis which means hardening of the arteries, and this leads to a build up of plaque and decrease in blood flow to the heart. (Shumaker 2006) For most cases, children only live to the age of 12 because they suffer a heart attack or stroke and their little bodies can not handle it. Progeria is a very rare disease that affects one in eight million new borns. The hard thing is, there is not yet a cure for Progeria. Progeria is not usually passed down in families. The gene change is almost always a chance occurrence that is extremely rare. Children with other types of “progeroid” syndromes which are not progeria may have diseases that are passed down in families. However, Progeria is a “sporadic autosomal dominant” mutation. This means that, for a family with one child with Progeria, non-twin siblings have the same chance of having a Progeria gene as any other child in any other family. In rare cases like one in four million births, Progeria can be passed down within a family.
Researchers are now testing mice to target why these genes are developing this way. Researchers have hypothesized that Progeria is caused by a de novo point mutation in exon 11 of LMNA. De novo is a mutation that you did not develop from your parents. Also they have said that by interfering with protein farnesylation, it would block the targeting of progerin to the nucleus envelop. (Yang 2005) To test this hypothesis the researchers came up with a gene targeted mouse model of Progeria. They tested the mice in their effect of a farnesyltransferase inhibitor on nuclear blebbing. By doing this, they found that the farnesyltransferase inhibitor mislocalized progerin away from the nuclear envelop. (Yang 2005) By that it did not cause abnormal shape cells.
Right now there is not a cure for Progeria, but there has been an on going clinical study that is hoping to have a cure by the end. Researchers have discovered that by using farnesyltransferase inhibitors (FTI’s) it can reverse the abnormality of the cells back to normal. Since May 7,2007 there has been 28 children participating in this clinical trial that is said to end October 2009. The children have seven visits in the two year period. They fly to Boston every four months to have testing done and receive a new supply of the FTI drug. Since April of 2003 the National Institute of Health and Progeria Research Foundation has made it possible to provide a scientific test to definitively diagnose children with Progeria.
It is hard to know for a parent that they are raising a child that could possibly only live until the age of 12. With all of the on going research they are hoping to find a cure soon. By October of this year researchers will know whether or not they have found a cure for Progeria.

Works Cited
1. Yang, Shao H. "Blocking Protein Farnesyltransferase Improves Nuclear Blebbing in Mouse Fibroblasts with a Targeted Hutchinson-Gilford Progeria Syndrome Mutation." National Academy of Sciences 102 (2005): 10291-0296.
2. McClintock, Dayle. “Hutchinson-Gilford Progeria Mutant Lamin A Primarily Targets Human Vascular Cells as Detected by an Anti-Lamin A G608G Antibody.” National Academy of Science 103 (2006): 2154-2159
3. Goldman, Robert D. “Accumulation of Mutant Lamin A Causes Progressive Changes I Nuclear Architecture in Hutchinson-Gilford Progeria Syndrome.” National Academy of Science 101 (2004): 8963-8968
4. Shumaker, Dale K. “Mutant Nuclear Lamin A Leads to Progressive Alterations of Epigenetic Control in Premature Aging.” National Academy of Science 103 (2006): 8703-8708

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