, , , ,

In a trinucleotide repeat a trio of bases – perhaps the infamous CAG triplet – repeats multiple times. Depending on the chromosome and location the number of repeats usually varies from normal to tolerable (more than normal but no known immediate effect) and then to carrier and symptoms. In some cases increases beyond the threshold level for symptoms can cause earlier onset or more severe symptoms. However, in a sequence of xxx CAG CAG CAG yyy the interpretation of the xxx and yyy triplets will not be altered by the CAG repeats because the vast bulk of DNA translation occurs in threes.

Enter the CNBP gene located on chromosome 3 in the q21.3 region. What repeats here is the CCTG sequence. Evidence suggests that up to 26 repeats is probably tolerable. Note that 4 x 3 = 3 x 4 which means here that if we have xxx CCTG CCTG CCTG yyy the xxx and yyy triplets will be interpreted correctly and the central bases will be CCT GCC TGC CTG. However, xxx CCTG CCTG CCTG CCTG yyy zzz should be read as xxx CCT GCC TGC CTG CCT Gyy yzz and so.

Also known as ZNF9, the CNBP gene provides instructions for making a protein called CCHC-type zinc finger nucleic acid binding protein. This protein has seven regions, called zinc finger domains, which are thought to bind to specific sites on DNA and RNA. The CNBP protein is found in many of the body’s tissues, especially the heart and the skeletal muscles. So far, the exact function of this protein is unknown, but it likely regulates other genes. The CNBP protein is necessary for normal embryonic development. A CNPB mutation that increases the repeats of the CCTG segment to higher than 75 (as of 2017 the most reported is more than 11,000 repeats) causes type 2 myotonic dystrophy.