P.O. Box 50030 London, ON N6A 6H8 info@rett.ca (519) 474-6877

Linking genetic findings to clinical symptoms in Rett syndrome

In 2014, the Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors had unanimously approved the funding of a $50,000 Research Grant to a joint grant application from Dr. Juan Ausio (Biochemistry and Microbiology, University of Victoria, BC) and Dr. John Vincent (Neurogenetics, University of Toronto). This was the first grant from The Hope Fund and was largest grant released at the time.

We are pleased to announce that with our support, their work, From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2 has been published in the Nature Journal “Scientific Reports”. A summary that explains the findings and context can be found below and to read the full article, please follow this link, www.nature.com/articles/srep38590/

Mutations in the MECP2 gene cause Rett syndrome (RTT). MeCP2 binds to chromocentric DNA through its methyl CpG-binding domain (MBD) to regulate gene expression.While it’s well established that single DNA changes can lead to Rett syndrome — one of the most common genetic forms of intellectual disability – a new CAMH study has for the first time linked DNA mutations directly to how severe the syndrome is among those affected.

The results could pave the way for improved diagnosis and potentially new treatments for Rett syndrome, which is marked by problems with communication, language, learning and physical coordination.

The study was led by Dr. John Vincent, Senior Scientist in CAMH’s Campbell Family Mental Health Research Institute, and PhD student and first author Taimoor Sheikh. It was published in the journal Scientific Reports in December.

The DNA in question is part of the MECP2 gene, which is made up of thousands of pairs of DNA – one part from our mother, one from our father. This DNA can be thought of as “letters” that create words to generate genetic instructions. In many cases of Rett syndrome, any one of about 160 known changes to these letters on the MECP2 gene can garble the words and then the instructions.

There’s a reason these single DNA changes have such serious effects: the MECP2 gene carries instructions for a fundamental protein in the brain. The MECP2 protein binds to DNA at various places, and then acts as a “switch” to turn nearby genes on or off.

The research team found that if the change, or mutation, occurred in a part of the protein where it disrupted the switch, the syndrome was more serious. Changes that were further from the parts of MECP2 protein that bind to DNA, instead affected how the protein interacted with other proteins. This led to milder symptoms.

“The discovery raises the possibility of finding compounds to treat Rett syndrome, if we could create a ‘patch’ to make the protein function the way that it’s supposed to,” says Dr. Vincent, who heads the Molecular Neuropsychiatry & Development (MiND) lab at CAMH.

In addition, the nature of each change – which “letters” were swapped out – also affected how serious the syndrome was, the researchers note. They used a series of tests to study MECP2 proteins, with 12 different mutations including many most commonly reported in girls with Rett syndrome.

Clinical implications

With further development, the findings could help in cases where Rett syndrome is suspected in a patient. Symptoms typically appear in girls before the age of two. Genetic screening would

yield information on the type of mutation, to predict the type and severity of illness, says Dr. Vincent. As there is currently no treatment for Rett syndrome, only symptom management, screening could point to where more supports are needed.

A study in boys

Another novel aspect of the study was the fact that it also focused on boys with MECP2 mutations. In boys, Rett syndrome is extremely rare. This approach provided researchers with a clearer picture of the effect of protein changes in terms of symptoms and severity.

The MECP2 gene is located on X chromosomes. As girls have two copies of X, those with Rett syndrome have a second unaffected MECP2 gene on the other X, which may compensate for the garbled instructions. This is seen by the fact that clinical symptoms of Rett syndrome vary greatly in girls.

As boys carry X and Y chromosomes, any mutation on the X has an even more serious effect. It’s believed that most such cases do not survive pregnancy or early infancy.

By studying 11 rare cases of boys identified with MECP2 mutations, the researchers were able focus on DNA changes and their molecular and cellular effects in relation to clinical severity, without any compensating effects of the second MECP2 gene on the other X chromosome.

Ultimately, they hope to find compounds to help treat Rett syndrome using an approach called “peptide panning.” It involves testing many different peptides, which are small pieces of proteins, to see which ones bind to the mutant MECP2 protein to help recover its normal functioning.

“By further developing the molecular and cellular tests used in our study, we hope to be able to predict the likely clinical outcomes for newly discovered MECP2 mutations, as well as screen for compounds that can make MECP2 protein with specific mutations revert back to its normal function,” says Dr. Vincent.

From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2.

Sheikh TI, Ausió J, Faghfoury H, Silver J, Lane JB, Eubanks JH, MacLeod P, Percy AK, Vincent JB.Published in Scientific Reports, 8th Dec 2016; funded through an ORSA grant to John B. Vincent and Juan Ausió.


 rettsyndrome-org                          netherland-rett


Communication services and support for individuals with Rett syndrome:

  • What are your experiences of communication services?
  • What support for communication do you receive?
  • What are the communication goals you are working towards with your child?
  • What works for you?
  • What could help you more?

As a parent/caregiver of someone with Rett syndrome, you can answer all of these questions and more in our survey for families. The survey is part of a larger project, funded by Rettsyndrome.org, to develop clinical guidelines for the assessment, intervention and longer-term management of communication in individuals with Rett syndrome. To make the guidelines truly international we need input from everyone affected by Rett syndrome, in as many countries as possible. This survey is for parents/caregivers. By working together and listening to everyone’s experiences we hope that communication services for all individuals with Rett syndrome will be improved. We can’t do it without you.

The survey has been online in English since October. It is now available in other languages, including:

Chinese (Mandarin), Danish, Dutch, Finnish, French, German, Hebrew, Italian, Lithuanian, Russian, Polish, Portuguese, Swedish.

If you speak another language and would find it easier to complete the survey in your own language, please contact the project coordinator to see whether we can make arrangements for this.

The survey can be completed on your computer or mobile device. It can be accessed via this link or by scanning the QR code:




If you have any queries, please contact:

Gill Townend (project coordinator)


The survey will remain active until the end of January 2017.

Please take time to add your voice and share your experiences with us.

Thank you,

The project team.

STARS Study ~ Is your child living with Rett Syndrome?

Is your child living with Rett Syndrome?

There is a research trial to evaluate the safety, tolerability and efficacy of an investigational drug in reducing respiratory abnormalities in patients with Rett Syndrome

Patients may be eligible who: 

* are 13 years and older,

* have a body weight of at least 25 kg (55 lbs), and

* experience multiple episodes of breath holding (apnea) while awake during the day

The study is being conducted at the following locations. If you are interested to learn more about this study please see the link, https://clinicaltrials.gov/ct2/show/NCT02790034?term=newron&rank=2  or contact the site nearest to you.

United States


University of Alabama at Birmingham

Call Jane Lane at 205-996-4927 or Email: jlane@uab.edu

Principal Investigator: Alan Percy, MD


Altman Clinical and Translation Research Institute, La Jolla, San Diego

Call Karen Ditslear at 858-246-2288 or Email: kditslear@ucsd.edu

Principal Investigator: Jeffrey Neul, MD, PhD


Rush Medical University Center, Chicago

Call Susan Rohde at 312-942-0079 or Email: susan_rohde@rush.edu

Principal Investigator: Peter Heydemann, MD


Texas Children Hospital, Houston

Call Mohammad Naqvi at 832-824-3634 or Email: Mohammad.Naqvi@bcm.edu

Principal Investigator: Daniel Glaze, MD

President’s Message ~ Extremely Thankful

As we begin the Holiday Season, I would like to take a couple of minutes to remember what is really important in our lives and to be truly thankful for all that we have. We all work very hard to ensure that our loved ones with Rett syndrome are properly cared for, supported and feel loved all the time. We do this to provide them with a quality of life that we know they deserve and I feel it is our privilege to give to them.

As the President of the Ontario Rett Syndrome Association, I am taking the time to really think about what I am truly thankful for and the blessings that I have been given in this past year. I have had the opportunity to be mentored in my new role by Terry Boyd. She is someone who is truly dedicated to all those living with Rett syndrome and their families, and who has shown this dedication for well over a couple of decades. I am thankful for our volunteer board of directors, who put in a lot of thankless hours to ensure that our association is successful and continues to grow and prosper. It is my privilege to lead this group of people who work together with passion towards a common goal, to make an impact on other people’s lives.

I am thankful for all of the fundraising and awareness initiatives that are led by our members which allow this organization to continue to financially support the three Rett Clinics in Ontario, support the maintenance of the Canadian Rett Syndrome Registry. This fundraising has also allowed us to release the largest Rett syndrome dedicated research grant in the history of O.R.S.A this year; $100,000. Without the continued effort and support from our members, their families, friends and many others, this association would not be able to thrive.

I am most thankful for my family and their support, which affords me the opportunity to attend meetings and put in the necessary work so that this organization can continue to grow and prosper. Elle has opened my eyes to so many things in this world. She often reminds me of a quote that I now treasure. “I thought I would to teach my child about the world. It turns out I have to teach the world about my child.” For this opportunity, I am extremely thankful.

Thank you for your support!

Thank you for your support of the Ontario Rett Syndrome Association (O.R.S.A.) in 2016.  It was a year of amazing accomplishments that could not have happened without your support.

In 2016, O.R.S.A. had several major accomplishments, all of which contribute towards an effort to ensure that children and adults with Rett syndrome are enabled to achieve their full potential and enjoy the highest quality of life within their community.

These include:

* Hosted the Rising Towards Tomorrow Conference in Ottawa with over 122 attendees traveling from 4 provinces to participate in the bi-annual educational event.

* Board of Directors has unanimously approved the funding of two $25,000 Research Grants from The Hope Fund in 2016.  The first $25,000 grant was awarded to Dr. James Eubanks from Toronto Western Hospital with and the second $25,000 grant was awarded to Dr Mojgan Rastegar from the University of Manitoba.

* Board of Directors unanimously approved the largest research grant in the history of Canadian Rett Associations. We were very excited to announce that The Hope Fund will be releasing a $100,000 research grant in 2017.

* Coordinated Rett Syndrome Awareness Day in Canada on October 29.  Buildings and homes across the country were lit purple for the night in solidarity.

* Continue to maintain and support the Canadian Rett Syndrome Registry.  This registry is important to families across Canada as future drug trials for Rett syndrome can only be implemented in Canada through an approved registry.

* Continued to make annual financial contributions towards the three Rett Syndrome Clinics in Ontario in order for them to continue to support the individuals living with Rett syndrome.

None of these accomplishments would have been possible without the efforts the volunteer Board of Directors at O.R.S.A. and your continued partnership with us.  We truly appreciate your love and support.

If you would like to make a year end donation by December 31, 2016, here are 2 ways for you to give:

1. MAIL- Please make cheques payable to Ontario Rett Syndrome Association and mail to (postmarked by 12/31/2014): P.O. Box 50030 London, ON N6A 6H8

2. ONLINE- Donate online at www.rett.ca