The Genetics of Polymicrogyria and Epilepsy

Children'S Hospital Boston, Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): As many as half of intractable seizures in the pediatric population are associated with malformations of the cerebral cortex. Recent studies have shown that many of these malformations result from the action of defective genes. The long-term objective of this project is to identify genetic defect of a specific neurological developmental disorder, bilateral frontoparietal polymicrogyria (BFPP). This recently identified clinical and neuroradiographic syndrome is due to bilateral malformation of the frontal and parietal cortex, while the remaining cortex is relatively spared. The goal of this proposal is to identify the gene for BFPP and study the role of this gene in cortical development. Our preliminary work mapped the BFPP locus to chromosome (ch) 16q12.2-21. Further studies suggested G protein-coupled receptor 56 (GPR56) is the potential gene for ch16-1inked BFPP. The proposed experiments will entail further characterization of BFPP syndrome and delineation of the role of GPR56 in cortical development. The Specific Aims include: 1) analyze genetic and clinical aspects of BFPP and BFPP-like syndromes, 2) mutational analysis of GPR56 in BFPP families and 3) characterization of the temporal and spatial pattern of GPR56 expression and generation of a mouse genetic model to examine the role of GPR56 in cortical development in vivo. The applicant is an MD/PhD who has completed her pediatric residency and neonatology fellowship. She earned her doctoral degree in molecular and cell biology studying the oncogenic properties of the wild type and mutated Kit receptors. Her mentor is Christopher A. Walsh, a Howard Hughes investigator who oversees a well-funded, well-equipped human and mouse cortical development and genetics laboratory. The research plan focuses on expanding candidate's knowledge of 1) genetic mapping and linkage analysis of a specific human brain malformation and 2) neurogenetics and molecular perspectives of cortical development.