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Progeria

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Submitted By qienah
Words 1184
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Maheetha Bharadwaj

Retrieved from the Progeria Research
Foundation Website: progeriaresearchfoundation.org Table of Contents
 Introduction and History
 Research of Erikkson et al. (2003)
 Causes: Mechanisms of mRNA Splicing
 Truncated Lamina A: Progerin
 Reverse Transcriptase Polymerase Chain Reaction
 Effects
 Treatment: Macro and Molecular
 Conclusion
 Bibiography

Introduction and History
 The Hutchinson-Gilford Progeria Syndrome (Progeria):






fatal disease that causes rapid aging
Only 1 in 8 million have this disease
First appearance: Hutchinson(1886)
Second appearance: Gilford (1904)
Only roughly 60 cases have been reported since: (Debrusk
1972, Brown et al. 1985 & 1986)
Erikkson et al. 2003—f rst research done to show actual i causes and effects

Research of Erikkson et. al (2003)
1. Out of 23 progeria, he found that 20 had a de novo mutation in LMNA gene(codes for nuclear Lamina A)
2. 18 out of 20: GGCGGT
1 out of 20: GGCAGC
1 out of 20: GAGAAG
The causes of Progeria in the other three cases are unknown 3. Creation of splice site

Mechanisms of mRNA Splicing
 Introns vs. Exons
 Donor acceptor pairs: GT-AG, GC-AG,

AT-AC, and GT-GG. (Fong et al. 2006).
The base pair progressions, GT, GC, and
AT have the potential to set of a splice site.  The splice site signals the excision of genetic information, leading to a deletion of 150 bps, and 50 amino acids.
Retrieved from: http://progeria2010researchproject.weebly.com/upload s/5/8/7/9/5879933/4698219.png

Truncated Lamina A: Progerin
Normal Wild-type Lamina contains two modif cations i (attachments): the farsynal group and the terminal group. Removal of two groupssuccessful integration into Nuclear Membrane.
Truncated Lamina A (Progerin): does not have terminal group. Cannot successfully integrate, and messes up integration of future Laminas.
Lamina keeps stable structure
And Progerin ruins it; nuclear lamina
Becomes lobular. Funky Nuclear Lamina 

Reverse Transcriptase Polymerase
Chain Reaction
 mRNA is copied into DNA by using a oligo dT primer.

Certain Heat-Stable DNA polymerase known as Taq polymerase is used for further transcription
 Denaturization of DNA
 mRNA primers added to separate DNA strands. Taq

polymerase starts to add on base pairs from the RNA primers. Total of 4 strands from 1 mRNA.

Effects

 Most prevalent of rapid aging symptoms: hair loss early ,

bulging out eyes, visible veins on body and head, Eggshaped head, atheroscleosis, deformed bones, calcium loss, and other growth deformities

Treatment
Macro and Molecular
Macro:
 Giving increased Growth hormone
 Give medication to reduce fat buildup in the Coronary
Arteries, or coronary bypass surgery
 Cao et al. (2011): rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. (ONIM)
Molecular:
 Glynn and Clover (2005): farnesylation inhibition
(ONIM)

Conclusion: Recap
 Progeria is a disease that causes rapid aging and is caused

by a base-pair substitution in the LMNA gene.
 Effects include abnormally projecting eyes and other growth defects
 Treatments include FTI’s that inhibit the progerin from reaching nucleus, increased supplements of Gh and calcium, and medication to reduce effects of atherosclerosis Thank You
Questions?

Bibliography
 Anonymous, 2007. New Clues for Treatment. The Pediatrics. (Retrived from:











http://www.medicalnewstoday.com/articles/69728.php
Badame A.J. (1989): Progeria; Archives of Dermatology : 125:1-5
Brown WT, Zebrower M, Kieras FJ (1985); Progeria, a model disease for the study of accelerated aging. Basic Life Science: 35:375-396.
Brown, W.T., Kieras, F.J., Zebrower, M., (1986). Urinary hyaluronic acid elevation in Hutchinson-Gilford progeria syndrome. Mechanisms of Ageing and Development.
35(1): 39-46.
Brunak, S., Engelbrecht, J., Knudsen, S., 2004. Prediction of human mRNA donor and acceptor sites from the DNA sequence. Journal of Molecular Biology. 220 (1):
49-65
Chong, A., Zhang, G., & Bajic, B.V., (2006). Information for the Coordinates of
Exons (ICE): a human splice sites database. Genomics. 84(4): 762-766.
Columbaro, M., Capanni, C., Mattioli, E., Novelli, G., Parnaik, V. K., Squarzoni, S.,
Maraldi, N. M., and Lattanzi G. Rescue of heterochromatin organization in
Hutchinson-Gilford progeria by drug treatment. Cellular and Molecular Life
Sciences. 62(22): 2669–2678.
ONIM

Bibliography
 Csoka, A.B., English, S.B., Simkevich, C.P., Ginzinger, D.G., Butte, A.J., Schatten,








G.P., Rothman, F.G., Sedivy, J.M. (2004). Genome-scale expression prof ling of i Hutchinson–Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Ageing Cell. 3(4):235-243
De Busk (1972). The Hutchinson-Gilford progeria syndrome. Journal of Pediatrics.
80 (4): 697-724.
Delbarre, E., Tramier, M., Coppey-Moisan, M., Gaillard, C., Courvalinand, J.C,
Buendia, B., (2006). The truncated prelamin A in Hutchinson–Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers. Human
Molecular Genetics. 15 (7):1113-1122.
Demmer, L., Sadeghi-Nejad, A. (2007). Growth hormone therapy in progeria.
Journal of Pediatrics for Endocrinal Metabolism. 20 (5): 633-637.
Dr. Margaret Hunt. “Real Time PCR”.
Erikkson et. al (2003) Recurrent de novo point mutations in lamin A cuase
Hutchinson-Gilford Progeria Syndrome. Nature 423(6937):293-298

Bibliography

 Fong, L.G., Frost D., Meta, M., Qiao, X., Yang, S.H., Coff nier, C., & Young, S.G. i 









(2006). A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse
Model of Progeria. Science. 311( 5767): 1621-1623.
Gilford H (1904). Progeria: a form of senilism. Practitioner 73:188-217.
Gilford H; Shepherd, RC (1904).
Ateleiosis and progeria: continuous youth and premature old age. The British
Medicine Journal. 2 (5157): 914–8.
Hutchinson J (1886). Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages in a boy whose mother had been almost totally bald from alopecia areata from the age six. Mediochir Trans 69:473-477.
Keay, A.J., Oliver, M.F., Boyd, G.S., (1955). Progeria and Atherosclerosis. Archives of Disease in Childhood. 30 (410-414).
Khalf a, M.M (1989). Hutchinson-Gilford progeria syndrome: report of a Libyan i family and evidence of autosomal recessive inheritance. Clinical Genetics. 35 (2):
125-132.
Manschot, W.A. (1950). A Case of Progerianism (Progeria and Gilford). Acta
Paediatrica. 39 (1): 158-164.

Bibliography
 Melissa A. Merideth, et al. (2007). Phenotype and Course of Hutchinson–Gilford










Progeria Syndrome. The New England Journal of Medicine. 358 (6).
Nathan, M., Mertz, L.M., Fox, D.K. (2001). Optimizing Long RT-PCR. Focus.
17(3): 78-80.
Navarro, C.L. et al. (2004). Expand+Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Human Molecular Genetics. 13 (20): 2493-2503.
Ozonoff, M.B., Clemett, A.R., 1967. Progressive Osteolysis in Progeria. American
Journal of Roentgenology. 100 (75-79).
Rautenstrauch,T., Snigula, F., Krieg, T., Gay, S., & Müller P. K. (1977). Progeria: A cell culture study and clinical report of familial incidence. European Journal of
Pediatrics. 124 (2):101-111.
Renee V. et al.: Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson–Gilford progeria syndrome: National Academy of Sciences. 3 (9):
3250-3255.
Sarkara, P.K., Shintonb, R.A. (1989). Hutchinson-Guilford progeria syndrome.
PostDoctorate Journal of Medicine. 77:312-317.

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