RSRF often needs pictures of individuals with Rett Syndrome to use in our brochures, website and fundraising materials. Please send your pictures either via email to monica@rsrf.org or by mail to RSRF, 4600 Devitt Drive, Cincinnati, OH 45246. Please note that we will not be able to return any pictures that are mailed to us. We are currently redesigning our brochure and look forward to seeing your photos.

The Strollathon is the signature event of RSRF.  It is a fun-filled gathering that increases public awareness of Rett Syndrome in local communities and raises much needed dollars for Rett Syndrome research.   This Spring, Strollathon events will be held in Pennsylvania, Connecticut and Massachussetts.  We encourage you to get involved and support the Strollathon in your regional area.  Whether you can bring a team of strollers, volunteer, help solicit sponsorship dollars or assist with in-kind donations, you are playing a key role in the success of the event.

Live too far from a Strollathon? Don't let distance keep you and your family/friends/colleagues from raising research funds. Join us in spirit with a "Virtual Team". With your support, there is no doubt that we will continue to accelerate the progress in finding treatments and a cure. For more information or to get involved, please click here or contact the Event Chairs below.

	Location			Date			Event Chair
	Harrisburg, PA		May 14		Kristy Kramer
	CT/NY/NJ		May 22		Monica Coenraads
	Cape Cod, MA		June 4		Jennifer and Justin Endres

Rett Syndrome is often misdiagnosed as autism since the disorders share some common symptoms. However, Rett Syndrome often includes a variety of movement disorders not seen in autism. Click here or on the title above to read the abstract.

At least 85% of individuals with Rett syndrome (RTT) have mutations or deletions affecting the coding sequence of exons 3 or 4 of MECP2, but the mutations in the remainder are still unknown.  A recently discovered MeCP2 isoform excludes exon 2 but includes exon 1. The prevalence of mutations in MECP2 exon 1 in individuals with Rett syndrome is not well known. Click here or on the title above to read the abstract.

CAMBRIDGE, MA - A new study by MIT scientists and colleagues confirms that melatonin is an effective sleep aid for older insomniacs and others. Misuse of the hormone had led some to question its efficacy, but the latest work (published in the February issue of Sleep Medicine Reviews) could jump-start interest in the dietary supplement and help more people get a good night's sleep.

In earlier research, scientists led by Professor Richard Wurtman, principal investigator for the current study, showed that only a small dose of melatonin (about 0.3 milligrams) is necessary for a restful effect. Taken in that quantity, it not only helps people fall asleep, but also makes it easier for them to return to sleep after waking up during the night--a problem for many older adults.

The researchers also found, however, that commercially available melatonin pills contain 10 times the effective amount. And at that dose, "after a few days it stops working," said Wurtman, director of MIT's Clinical Research Center and the Cecil H. Green Distinguished Professor. When the melatonin receptors in the brain are exposed to too much of the hormone, they become unresponsive.

As a result of these inadvertent overdoses, "many people don't think melatonin works at all," said Wurtman, who is also affiliated with the Department of Brain and Cognitive Sciences. This belief, coupled with potentially serious side effects related to high doses such as hypothermia, has earned the hormone a bad reputation in some quarters--"and something that could be very useful to a lot of people isn't," said Wurtman, who said that he and his wife have been taking melatonin every night for about a year now.

To determine conclusively whether melatonin works or not, the scientists in the current study analyzed 17 peer-reviewed scientific papers about the hormone. To be included in this study, or meta-analysis, the experiments reported in each paper had to satisfy specific criteria. For example, each had to be placebo-controlled and include objective measurements on at least six adult subjects.

"A meta-analysis essentially tells 'yes' or 'no'--that a treatment does or does not have a significant effect," Wurtman said. "When a meta-analysis says 'yes,' there should no longer be any controversy about whether the treatment works."

The melatonin meta-analysis delivered a definitive "yes."

Wurtman notes that some of the 17 studies included in the analysis involved very high doses of the hormone over long periods, a "situation where we know it's not going to work." Yet the meta-analysis still showed that the hormone's positive effects on sleep "are statistically significant."

When Wurtman first discovered the efficacy of small doses of melatonin, he and MIT patented its use for dosages up to one milligram. Because the FDA defined the hormone as a dietary supplement, however, manufacturers were free to sell it in much higher dosages, "even though we knew they wouldn't work," Wurtman said.

As a result, until recently the hormone was commercially unavailable to the public in small doses. "People who knew that small doses were best often bought the high-dose pills, then divided them with a knife," Wurtman said. "But that's not very accurate."

The company Nature's Bounty has since licensed the work, and now the hormone is easily available in the effective dosages.

Wurtman's colleagues in the meta-analysis work are Amnon Brzezinski of Hadassah-Hebrew University Medical Center in Israel; Mark G. Vangel, a visiting scientist at the Clinical Research Center; Gillian Norrie and Ian Ford of the University of Glasgow in Scotland; and Irina Zhdanova of the Boston University School of Medicine.

Until recently the scientific community believed that "one gene made one protein". When the human genome revealed that in fact there were about 30,000 genes but 120,000 proteins it became evident that the old paradigm needed revisiting. In April of 2004 it was discovered by Adrian Bird and Berge Minassian that the MECP2 gene actually made a second MeCP2 protein. The process by which one gene can make multiple proteins is called "alternative splicing". To read more click here.

INTRODUCTION. Rett syndrome is a progressive neurodevelopmental disorder with onset in early childhood occurring almost exclusively in females and caused by mutations in methyl-CpG- binding protein 2 (MECp2) and is one of the most frequent causes of mental retardation in females. Regression is a defining feature of Rett syndrome and during the regression period the patients develop autistic behaviour. This is the reason why Rett syndrome has been classified as a pervasive developmental autistic spectrum disorder. However movement disorders are so exuberant, characteristic and unique in Rett syndrome that is very difficult to an experienced clinician mistake both situations. DEVELOPMENT. We can define Rett syndrome as a condition which manifests in the majority of the cases as a hyperkinetic movement disorder and progresses (at varying rates) to a bradykinetic disorder. The aim of this publication is to characterize and describe movement disorders in Rett syndrome based on a revision of the literature and the personal experience of the author.

Abstract

Introduction: At least 85% of individuals with Rett syndrome (RTT) have mutations or deletions affecting the coding sequence of exons 3 or 4 of MECP2, but the mutations in the remainder are still unknown.  A recently discovered MeCP2 isoform excludes exon 2 but includes exon 1.  The prevalence of mutations in MECP2 exon 1 in individuals with Rett syndrome is not well known.

Methods: We sequenced exon 1 from genomic DNA of 63 affected individuals, 38 with classic RTT and 25 with atypical RTT, who previously tested negative for mutations involving exons 2, 3 and  4.  These individuals belong to an original cohort of 321 affected females.  We studied X chromosome inactivation (XCI) using the androgen receptor assay on peripheral blood leukocyte DNA of patients with an identified mutation.

Results: We identified a de novo mutation at the intron  splice donor site (c.62+1delGT) in a classic RTT patient.  XCI studies revealed 68%:32% skewing with preferential inactivation of the paternal X.  A second patient with atypical RTT has an 11bp deletion (c.47_57del), creating a frameshift and premature stop codon (p.Gly16GluƒsX36) and has random XCI.  Surprisingly, although exon 1 belongs to the major MeCP2 isoform, mutations of this exon account for only 1/321 (0.3%) of classic RTT and 2/63 (3.1%) of all “mutation-negative” RTT in this study.

Conclusion: Mutations in MECP2 exon 1 thus appear to be rare. However, inclusion of exon 1 should be incorporated into a comprehensive DNA diagnostic testing strategy for Rett syndrome.