Jennifer Sloan

Dr. Jennifer Bain (MD, PhD) found point mutations in the gene that codes for Heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2) on the X chromosome that correlate with a neurodevelopmental disorder. Most of these mutations are in the putative nuclear localization sequence of the protein. These mutations were thought to be fatal in males, but Harmsen et al. and Jepsen et al. found males with mutations in HNRNPH2 and a similar phenotype to the previously identified females. We additionally questioned if these mutations inhibit nuclear localization or not, as that is the current hypothesis. We focused on mutation P209L, as different mutations may have different mechanisms. We used site directed mutagenesis to clone the mutation into the plasmid vector. We then used RFLP and Sanger sequencing to verify the mutant. We transfected the mutant into human neural progenitor cells, which we terminally differentiated into neurons and astrocytes. We performed a western blot, fractionated western blot, and immunofluorescent chemistry to detect the presence and location of the mutated HNRNPH2.