HNRNPH2 mutations have been detected in patients and are considered pathogenic, or disease causing . Heterogeneous Nuclear Ribonucleoprotein H2, or the abbreviation HNRNPH2, is a gene, found on the X chromosome of an individual.

This gene is part of the HNRNP family of proteins which are found mainly in neurons (major components of the brain and spinal cord of the central nervous system), mostly located in the nucleus (a central organelle of a cell, containing most of the cell’s DNA).

What exactly has happened on the HNRNPH2 gene of these girls?

DNA on a gene is a chain of amino acids that have been likened to a recipe card. Certain ingredients are needed for the expected result. Similarly, on our genetic codes, certain amino acids are expected to be present for normal/expected development to occur. Each of our daughters have been identified as having a “mis-write” or an improper ingredient on a particular location on the HNRNPH2 gene. There is an unexpected “change” or “variation” in a sequence of amino acids that normally stays the same, across people and other organisms that are known to have an HNRNPH2 gene.

The area on the HNRNPH2 gene called the nuclear localization sequence, or the NLS, is the area where our daughters’ mutations have been identified.  This is of great significance.

A nuclear localization sequence (NLS) is an amino acid sequence (an area of amino acids) which “allows” proteins created in the cytoplasm of a cell to enter the nucleus by nuclear transport.  Think of the NLS as the UPS center that will get deliveries (proteins) to where they need to go.

The mutation or mis-spelling of an amino acid in the NLS, which our girls are identified as having, is most likely disrupting the entrance of the protein into the nucleus.  Deliveries of vital proteins needed for proper development are not being made.  The proteins or “packages” needing to be delivered are left clogging up the cytoplasm, rather than getting delivered into the nucleus.

This is a simplistic summary of HNRNPH2 mutations.  A more detailed description of the science behind HNRNPH2 mutations is under construction and will include graphics to help conceptualize these ideas.