In 1999 Huda Zoghbi of Baylor College of Medicine identified mutations in the MECP2 gene as the leading cause of Rett Syndrome (RTT). The MECP2 gene can be envisioned as a book with four chapters, called exons. By splicing these exons into different configurations genes can make alternate forms of a protein. The novel form of the MeCP2 protein shares exons three and four with the original form but is missing exon two. Furthermore, the Canadian researchers report the first identified mutations in exon one.
Berge Minassian, the lead author from The Hospital for Sick Children, states, "The human genome has been sequenced completely, yet to our ongoing amazement, the genetic information that defines who we are is much more complex than the mere DNA sequence. We are finding that many, if not most genes shuffle their sequences around to create various proteins with unique functions. We have discovered a new form of the MeCP2 protein which may turn out to be the more important form in RTT. This opens a whole new avenue of RTT research. One day, this and other similar paths will lead us to a full understanding, and hopefully a treatment for this devastating disorder."
RTT is a severe neurological disorder diagnosed almost exclusively in girls. Children with RTT appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.
"It is most intriguing that the alternate MeCP2 protein is more abundant in the brain. Understanding its function and how it relates to the symptoms seen in RTT are the next key questions that must be answered. In the short term, this discovery may help identify exon one mutations in the cohort of Rett patients who, to date, have tested negative." stated Monica Coenraads, Director of Research for the Rett Syndrome Research Foundation (RSRF). Founded in late 1999, RSRF is the world's leading private funder of RTT research.
"This began with a simple exploratory experiment by an undergraduate student. The persistence of Dr. Minassian and the rest of the group has led to the discovery of a crucial clue in the understanding of RTT. It will now be important to prove the newly described protein's role in the disease. However, having seen first-hand the impact RSRF funding continues to make promises that one day basic research findings such as this one will eventually translate into clinical applications that will help these beautiful children," said co-author and RSRF Scientific Advisory Board member, Stephen Scherer.
For more information on RTT and RSRF please visit our website at www.rsrf.org.