Rett Gene Discovery: Ten-Year Anniversary
Tenacity, talent and pure luck coincided ten years ago this week in a crucial experiment that forever changed the landscape of Rett Syndrome research.
Dr. Zoghbi examined her first patient with Rett Syndrome in the mid 1980’s and was so emotionally and intellectually hooked that she decided to put her nascent neurology clinical practice on hold and move instead into basic science. Her ambitious goal to locate the gene mutations responsible for this puzzling disorder was successfully realized sixteen years later.
Because Rett Syndrome is a sporadic disorder “gene hunters” could not employ traditional strategies to identify the culprit gene. Fortunately significant clues came courtesy of several families with multiple affected members and the location was narrowed to a specific section of the X chromosome – Xq28. What followed was a painstaking candidate gene approach analyzing each of the hundreds of genes located on Xq28. Visit an earlier blog post to read in Dr. Zoghbi’s own words the details of the gene discovery.
During the summer of 1999 my daughter, then three years old, had been diagnosed for less than a year. As any parent of a newly diagnosed child will testify the year had been marked by a rollercoaster of emotions. With the shock and the grief came also the urgent desire to understand the lay of the land in current Rett research and how I might help to speed things along. I spent my days juggling Chelsea’s therapy visits, caring for my 5-month-old son and speaking to as many scientists as I could.
Late one night in early September I received an instant message from a fellow mom who had taken her disabled child to see a well-known autism spectrum disorder neurologist in the Boston area earlier that day. The doctor mentioned that the “Rett gene” had finally been found. I had heard similar claims in the past year that turned out to be unsubstantiated rumors, so I spent the next few days doing detective work. To my surprise and delight, this time it was true. A few days later I spoke to Dr. Zoghbi and she confirmed the wonderful news. A few excruciating weeks followed during which the discovery had to be kept under wraps until the embargo was lifted, and the paper was published inNature Genetics on October 1, 1999.
I spent hours on PubMed learning about this gene/protein with the strange name, methyl CpG binding protein 2. Eager to identify the leading labs, I poured through every publication on the subject. Two names flew out at me: Adrian Bird and Alan Wolffe. That same week I called them both and a few months later had an opportunity to meet them at Rett Syndrome meeting in Washington DC. Both quickly became cherished mentors. I was devastated to learn in May of 2001 that a traffic accident in Rio de Janeiro had claimed the life of Dr. Wolffe at the age of 41, leaving behind two young children and a devoted wife.
It is hard to convey to parents and relatives whose children were diagnosed after the gene discovery the excitement felt by the Rett community. For me it was the realization that the limited world of Rett research was about to burst wide open and that we would soon welcome scientists from the fields of epigenetics, DNA methylation, X inactivation, gene therapy and more. It was exhilarating to think that Rett might be able to leverage decades of research already underway in these many laboratories.
It was this excitement and promise that prompted me and five other parents to start the Rett Syndrome Research Foundation in the fall of 1999. During the next eight years RSRF’s funding contributed to nearly every major publication in the field culminating in Adrian Bird’s reversal experiments of 2007. I left shortly thereafter to establish RSRT.
Scientists and their institutions and funding agencies often trumpet any progress as a breakthrough. In reality true breakthroughs are few and far between. They are always unpredictable and they indelibly change the course of research. The Zoghbi Lab’s discovery on that hot, humid Houston day in mid-August certainly fits the bill.
The Rett community owes a tremendous debt of gratitude to Dr. Zoghbi, not only for her fortitude during the difficult 16-year search for the gene, but also for the plethora of key scientific papers she has written since.
I often hear Dr. Zoghbi described as one of the most accomplished female neuroscientists of our time. Her impressive body of work and the respect she commands on the international scientific world stage have played an enormous part in making Rett Syndrome a high-profile disorder.
Over the ensuing years I have been fortunate to count Dr. Zoghbi as an advisor and a friend. I ask the Rett community to join me in congratulating her and her colleagues, in particular Ruthie Amir, on the 10-year anniversary of their momentous discovery.
May we all have much to celebrate before another decade has passed.Share this article: