Understanding the biological impact of HNRNPH2 mutation causing MRXSB
Many neurodevelopmental disorders are often related to X-linked genes. One such gene is HNRNPH2, which encodes for the HNRNPH2 protein. HNRNPH2 is part of the heterogeneous nuclear ribonuclearproteins (HNRNP) family, which act as a shuttle between nucleus and cytoplasm and controls mRNA splicing. Past literature shows that de novo hemizygous mutation in HNRNPH2 previously identified in females have been shown to cause mental retardation, X-linked, syndromic, Bain-type (MRXSB). Mutations in HNRNPH2 were also thought to be embryonically lethal in males. In this study, we investigate a male patient who has a mutation in HNRNPH2 and has the same MRXSB phenotype. The patient has a mutation in the nuclear localization sequence (NLS) of HNRNPH2 which affects the proteins ability to enter the nucleus to perform its job of splicing. Past literature supports the claim that this region is of primary importance to the protein and a mutation in the NLS would directly cause the MRXSB phenotype. This project focuses on defining the biological effects of the mutation from patient derived fibroblast cells. From these cells, we were able to take immunofluorescent images to show our patient’s mutation in the NLS does affect the HNRNPH2 protein localization in nucleus. Furthermore, through protein modeling on I-TASSER, we found structural changes due to the mutation within the NLS, proving the significance of the NLS beyond the literature.
