Luca Bartolini, MD

Assistant Professor of Pediatrics, Assistant Professor of Neurosurgery, Assistant Professor of Neurology


Advance-CTR Pilot Projects Program (2020)

"Epilepsy and Neurocognitive Function in Patients with Neurogenetic Disorders"
Co-PI: Brian Kavanaugh, PsyD (contact PI)

Human genetic disorders offer a powerful approach to understanding complex brain processes such as neuropsychiatric disease and therapeutics. We have been actively studying a newly-recognized X-linked disorder affecting boys, now called Christianson syndrome (CS). CS arises due to loss-of-function mutations in the X-linked endosomal Na+/H+ exchanger 6 (NHE6, also known as SLC9A6). Importantly, we have also recently reported that female carriers of NHE6 mutations appear to be susceptible to a complex neuropsychological phenotype with incomplete penetrance and variable expressivity. The overall objective of this application is to define target symptoms resulting from NHE6 mutations in male probands and female carriers, as well as to identify neurobiological predictors of disease progression. Our central hypothesis is that the NHE6 mutation manifests as distinct, progressive phenotypes in male probands and female carriers; however, symptoms seen in males may be more moderate and variable in female carriers. We will examine the epilepsy phenotype and electroclinical features in male probands with NHE6 mutations (Aim 1) and the neurocognitive phenotype in female mutation carriers (Aim 2). This study will form the foundation for a natural history study and eventually treatment trials.