Catherine Astrid Brownstein, MPH, PhD
2017 DICP Faculty Fellowship Recipient
Catherine Astrid Brownstein, MPH, PhD Instructor, Harvard Medical School; Department of Pediatrics, Boston Children’s Hospital
Mentor: Joseph Gonzalez-Heydrich, MD, Associate Professor of Psychiatry, Harvard Medical School, Boston Children’s Hospital
Division Chief: Christopher Walsh, MD, PhD, Bullard Professor of Pediatrics and Neurology, Harvard Medical School; Chief, Division of Genetics and Genomics, Boston Children’s Hospital
“Using Whole Genome Sequencing to Find Non Coding Region Mutations Responsible for Very Early Onset Psychosis”
Studying extreme forms of a condition gives a lot of information that can be applied to more typical forms of a condition. Patients with Very Early Onset Psychosis (VEOP) are rare, having a prevalence of around 1 in 40,000; however, studying these extremely severe cases is important for understanding mental health as a whole (including autism and adult onset schizophrenia).
Dr. Gonzalez-Heydrich and I have been performing exome and chromosomal microarray (often called CMA) genetic testing on patients with VEOP with success, leading to the discovery of some new genes for this condition. However, there is a subset of patients for which this approach has been unsuccessful in producing gene candidates. The DICP award allows us to perform a more complete genetic test, called Whole Genome Sequencing (abbreviated as WGS) on these patients. WGS will allow us to find mutations that we would not be able to detect in exomes or CMAs. Aim 1 is to perform WGS on VEOP proband-parent sets for whom CMA and WES have failed to identify strong candidate mutations, and to use a series of computational tools to identify additional candidate variants that might contribute to their condition. Aim 2 is to manually inspect genomic regions for repeat expansions found patients with frontotemporal dementia (FTD), as we have preliminary data suggesting an overlap of VEOP with FTD. It has recently become appreciated that these non-exonic variants can be transcribed and translated making toxic gain of function products that contribute to neural degeneration.
Dr. Brownstein is a Research Associate in Genetics and Genomics, Instructor in Pediatrics, and the Manager of the Molecular Genetics Core Facility at Boston Children’s Hospital. As the Scientific Director for the Manton Center for Orphan Disease Research and specializing in gene discovery, Dr. Brownstein has been instrumental in the elucidation of several new disease genes for conditions such as intellectual disability, nemaline myopathy, very early onset psychosis, SIDS, and hypophosphatemic rickets. Her current work focuses on advancing the fields of next generation sequencing and analysis, as evidenced in her management of the international CLARITY and CLARITY Undiagnosed competitions.