Brain Development Research Program
at the University of California, San Francisco
Dr. Elliott Sherr and his collaborators at UCSF are studying the genetic causes of disorders of cognition and epilepsy,
as well as the brain malformations associated with these disorders. Our focus is on polymicrogyria (PMG), Dandy-Walker malformation (DWM), and disorders of brain development that affect the corpus callosum
(ACC/DCC). We are studying the clinical features of these disorders to better understand the problems faced by individuals with these disorders. The goal of our research is to use a better understanding of the underlying genetic causes as a foundation to develop better treatments for these groups of patients.
What are the genetic causes of ACC, PMG, and DWM? For the vast majority of individuals with these disorders, we do not know the cause(s), genetic or otherwise. We are taking multiple approaches to discover the genetic causes of ACC, PMG, and DWM in our study participants.
- We are using a novel technique called "comparative genomic hybridization microarray" to detect subtle chromosome changes that can’t be seen under the microscope. We have already detected chromosomal changes in ACC patients using this technique. We have begun to use a newer version of this microarray, which is ten times more sensitive.
- In collaboration with Drs. Bristow and Pennacchio at the Joint Genome Institute (a Department of Energy funded genomic group), we are sequencing genes that cause ACC in animal models to determine whether these genes cause ACC in people.
- We are also collaborating with Dr. Bill Dobyns at the University of Chicago, Drs. Lynn Paul and Ralph Adolphs at CalTech, and Dr. Warren Brown at the Fuller Graduate School of Psychology in Pasadena, who are conducting similar studies. This collaboration allows us to expand our resources and limit duplicate testing and analysis.
- We are examining MRI scans obtained in the diagnosis of ACC, PMG, or DWM and asking whether these findings correlate with clinical outcomes. We have preliminary evidence that the absence of the anterior commissure and that a significant loss of white matter volume correlates with a worse outcome for ACC individuals.
- For individuals who come to UCSF, we are performing a new MRI technique called diffusion tensor imaging (DTI) that allows us to see the white matter tracts that connect the different parts of the brain.
In addition to single individuals with these conditions, we are seeking to enroll large families in which more than one person has ACC, PMG, or DWM. This approach has been used quite successfully to discover the causes of such diseases as cystic fibrosis and hemophilia.
Do MRI findings correlate with issues that ACC, PMG, and DWM individuals face? We would like to know whether certain MRI findings correlate with the severity of problems confronted by these patients or whether certain clinical issues like seizures occur when a particular set of brain development problems are seen on MRI. We are studying this question currently through two approaches:
Aicardi Syndrome—In addition to ACC, individuals with Aicardi syndrome usually have severe epilepsy (including infantile spasms), problems with brain development (including ACC, also polymicrogyria, heterotopia, cysts and other cortical dysplasias), problems with eye development (chorioretinal lacunae, optic colobomas) and typically severe neurodevelopmental impairment. Aicardi syndrome has been reported only in females or in males who have two X chromosomes. We propose to use the techniques explained above in the hopes of identifying the Aicardi syndrome gene.
How to enroll in our study: Anyone with agenesis or dysgenesis of the corpus callosum,
polymicrogyria, or Dandy-Walker malformation
is eligible to enroll. To begin the enrollment process, please contact Zoe Strominger at 415-502-8039 or StromingerZ@neuropeds.ucsf.edu.
Please also obtain a brain MRI of the affected individual and arrange for that scan to be sent to us for review. Once we have reviewed the scan, we will complete the enrollment process. We will request:
- Blood samples from the individual, parents and perhaps other close family members
- MRI Scans (for recent scans, sending a CD copy is usually easiest)
- Medical History (including neurologic, ophthalmologic and genetic information)
- Psychometric testing results
Most of this information can be obtained over the phone and through the mail. Location does not hinder participation in our study. If, however, you live in the Bay Area or plan to visit San Francisco, please contact us so that additional study opportunities can be arranged.
Participation in our research is completely voluntary and without expense. If you travel to UCSF, transportation costs can be partially defrayed. Our research is approved by the Committee on Human Research at UCSF (http://www.research.ucsf.edu/chr/), and supported by the NIH, March of Dimes and UCSF.
