Rett Syndrome. Presentation by: PHM142: Nov. 16, 2012 Brian Talan Chia Hui Chung Hardit Khuman Priya Patel . PHM142 Fall 2012 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson. Overview:.
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Presentation by: PHM142: Nov. 16, 2012
Chia Hui Chung
PHM142 Fall 2012
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
(Simmons, 2008 adapted from Egger, 2004)
Figure A. MECP2 gene structure, showing the alternative splicing patterns that yield the A and B isoform of the MeCP2 protein
The A splicing variant includes part of exon 2 but not exon 1, and translates to the MeCP2A (or β) isoform, of 486 amino acids
The B splicing variant includes exon 1 but not exon 2, and translates to the MeCP2B (or α) isoform, of 498 amino acids
MeCP2B is the predominant isoform in the brain, whose amino acid sequence structure is shown in Figure B.
MBD: Methyl-CpG binding domain, NLS: Nuclear Localization Signal, TRD: Transcription Repression Domain, WW domain binding region: group II WW binding domain ( specific binding to WW domains of splicing factors (e.g. formin binding protein II, and HYPC (Huntington yeast protein C)
MECP2B is now called MECP2E1; MECP2A is now called MECP2E2
(Zachariah and Rastegar, 2012)
MeCP2 originally thought to act globally in the repression of transcription
(Weaving et al, 2005)
Histone Deacetylase co-repressors
Dlx5 and Dlx6 exhibited 2x expression in MeCP2-null mice brains
(Zachariah and Rastegar, 2012)
"Rett Syndrome Fact Sheet." Ninds.nih.gov. Office of Communications and Public Liaison National Institute of Neurological Disorders and Stroke, Nov. 2009. Web. 15 Nov. 2012. <http://www.ninds.nih.gov/disorders/rett/detail_rett.htm>.
"Rett Syndrome." Nichd.nih.gov. Eunice Kennedy Shriver National Institute of Child Health and Human Development, 8 Feb. 2010. Web. 15 Nov. 2012. <http://www.nichd.nih.gov/health/topics/rett_syndrome.cfm>.
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Kliegman, Robert. Nelson Textbook of Pediatrics. Philadelphia (Pa.): Elsevier Saunders, 2007.References:
Simmons, Danielle. “Epigenetic Influences and Disease”. Nature Education 1.1 (2008).
Zachariah, Robby Mathew and Rastegar, Mojgan. “Linking Epigenetics to Human Disease and Rett Syndrome: The Emerging Novel and Challenging Concepts in MeCP2 Research.” Neural Plasticity 2012. 415825 (2012): 1-10.
Weaving, L S, Ellaway ,C J, Gécz, J, and Christodoulou, J. “ Rett Syndrome: clinical review and genetic update”. Journal of Medical Genetics 42.1 (2005): 1-7.
“Rett Syndrome”. Genetics Home Reference. US National Library of Medicine, 12 November 2012.
“Rett Syndrome”. Eunice Kennedy Shriver National Institute of Child Health and Human Development 06-5590 (April 2006).