Abstract
Solving the mystery of epilepsy and mental retardation limited to females (EFMR)
Kim Hynes
PhD candidate, Department of Genetics, Children, Youth and Women’s Health Service and University of Adelaide / SA Pathology
Epilepsy and mental retardation limited to females (EFMR) is a very interesting disorder that leads to seizures in infancy and cognitive impartment in females. We have recently identified that EFMR is caused when females inherit a disrupted version of the gene PCDH19. PCDH19 is a cell-adhesion molecule believed to function in brain cell connections by passing messages through the brain. This is the first time that PCDH19 or any of its close relatives has been associated with seizures and cognitive impairment. This finding may pave the way to identifying additional PCDH genes in similar conditions where brain function is disrupted.
This discovery was particularly surprising because the gene PCDH19 occurs on the X-chromosome. Defects of X-chromosome genes typically cause disease only in males. Females have two copies of the X-chromosome and are typically unaffected by X-chromosome disorders as they have a “back-up” normal copy of these genes that can compensate for the defective copy. Unfortunately the back-up copy of PCDH19 in EFMR is unable to compensate and protect females from EFMR. Through additional experiments we hope to identify why the back-up copy of PCDH19 cannot compensate in affected females.
PCDH19 should be could as a possible reason for why females suffer from epilepsy and mental retardation particularly in families where there are affected females but no affected males. Females that fit these criteria should consider having genetic testing to see if they do have a disruption to their PCDH19 gene.
