Boston - A mutation in the MYMK gene, which leads to reduced production of the protein "Myomaker", is the cause of Carey-Fineman-Ziter syndrome, an extremely rare congenital muscle disease. The researchers hope in Nature Communications (2017; doi:) that injecting the correct version of the gene into the diseased muscles could alleviate the symptoms of the disease.
The gene defect was identified by sequencing the exome, i.e. the Decoding of all protein-coding genes, discovered in six patients from three unrelated families. In all three families, (different) mutions in the MYMK gene were found in those affected, which led to reduced production of the protein "Myomaker".
The total loss of production was not compatible with life for so-called knock-out mice for long time. There was complete failure of muscle development. With the CRISPR / Cas9 technology, Silvio Alessandro Di Gioia of the Boston Children's Hospital and staff have simulated the individual genetic defects of the patients in zebrafish.
The affected fish showed growth disorders and abnormal muscle development, including the jaw deformities typical of Carey-Fineman-Ziter syndrome. In the fish, the researchers were able to reduce the degree of muscle weakness by injecting the genes into individual muscles. It is unknown whether similar therapy would be effective in humans.
The disease is extremely rare. Only 20 patients were described in the literature worldwide - before the genetic defect was discovered. The researchers searched for other diseases among more than 300 patients with similar symptoms and found two cases. Both of them had been diagnosed with Möbius syndrome, the genetic cause of which has not yet been found.