Gene Responsible For Developmental Disorder Identified; Discovery Could Lead To New Therapies For Smith-Magenis Syndrome

The finding is documented in the March 24 issue of Nature Genetics, a prestigious peer-reviewed British journal.

SMS is a chromosome microdeletion syndrome that is characterized by a very distinct series of physical, developmental and behavioral features, including varying levels of mental retardation, cranio-facial abnormalities, sleep disturbances and self-injurious behaviors.

Because the disease is manifested in so many ways and is associated with a chromosomal deletion that includes many genes, it was always assumed that more than one gene contributed to the disorder, said researcher Sarah Elsea.

"This disorder was assumed to be a contiguous gene syndrome," said Elsea, an assistant professor in the departments of Pediatrics and Human Development and Zoology. "However, our data show that primarily one gene contributes to the phenotype."

What Elsea and colleagues found was mutation on a gene – identified as retionic acid induced 1 (RAI1) – that prevents the production of normal protein from that gene.

"The result of this mutation is that the protein can't be formed properly," she said. "Individuals with SMS have one normal functioning RAI1 protein from one chromosome, but from the other chromosome they are not getting this protein function at all."

Because SMS is a sporadic genetic disorder, prevention is pretty much out of the question, Elsea said. However, early diagnosis of the disorder can lead to improved outcomes.

"I think that in the future, if we understand what this gene, this protein, does and how it interacts with other proteins in the cell, we might be able to develop some kind of drug therapy that might help deal with the behaviors a little better," she said. "Early diagnosis is beneficial because the child needs the most appropriate early interventions."

Elsea said it's also very important for parents of SMS children to have a diagnosis.

"They need to know that it's not something that is preventable," she said. "Parents are sometimes blamed for the abilities or inabilities of their children and that's unfortunate. A proper diagnosis is crucial for the well-being of the family."

It is estimated that SMS occurs in one of every 25,000 births.

"We're hopeful this study could have wider-ranging effects on the study of sleep disorders and other behavioral problems, as well as provide more insight into early development of the fetus," Elsea said.

Contributing to the research were Rebecca Slager and Christopher Vlangos, doctoral students in the MSU Genetics Program; Tiffany Lynn Newton, a junior in MSU's Howard Hughes Undergraduate Research Support Program; and Brenda Finucane of the Elwyn Training and Research Institute of Elwyn, Pa.

The research was funded by a grant from the National Institute of Child Health and Human Development.