Adrian Bird originally cloned the MECP2 gene in 1992 while in Vienna, Austria at the Institute for Molecular Pathology. In October of 1999 Huda Zoghbi of Baylor College of Medicine and the Howard Hughes Medical Institute announced that mutations in the MECP2 gene were the leading cause of Rett Syndrome (RTT).
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.
The MECP2 gene, which is believed to regulate gene expression, 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.
"This is a small but significant step forward in our understanding of MeCP2, as the new form is the most abundant type of MeCP2 in human brain. We need to keep in mind though that the old and new forms of MeCP2 only differ in 19 out of 500 subunits. In other words, they are 97% identical. It will now be interesting to determine if the slight difference in structure affects MeCP2 function," shared Bird.
"The finding that this new form of MeCP2 is the most abundant form of MeCP2 in the brain is interesting and raises questions about potential functional differences between the two proteins," said Zoghbi.
"Currently about 15 % of patients with a clinical diagnosis of RTT are testing negative for mutations in the MECP2 gene. This development may help to further identify mutations in exon 1. Incorporation of this clinical testing will be of importance to affected families and may provide scientific insight," stated Monica Coenraads, Director of Research for the Rett Syndrome Research Foundation (RSRF).
Bird is the Chairman of the Scientific Advisory Board of RSRF. Founded in 1999 RSRF is the world's leading private funder of RTT research. For more information on RTT and RSRF please visit our website at www.rsrf.org.