Mental retardation, X-linked, syndromic, Bain type: HNRNPH2, R206Q, and nuclear localization
Mental retardation, X-linked, syndromic, Bain type (MRXSB) occurs through variations in the HNRNPH2 gene, and its shared neurodevelopmental phenotypes involve seizures, feeding problems, and hypotonia. Dr. Jennifer Bain postulated that the mutation caused the disorder through the protein’s inability to translocate to the nucleus. However, our lab had data that suggested Arg206Tyr, one of the identified mutations, does not inhibit the nuclear localization of the protein. To follow up with this study, Arg206Gln, another identified variation, was examined using site-directed mutagenesis, transfection, western blotting, and immunofluorescent chemistry. Possible mechanisms as to how this disease comes about include: the inhibition of the interaction between Transportin, an import receptor, and the nuclear localization sequence of the protein; or the inhibition of alternative splicing by affecting splicing regulatory elements.