Dishevelled Segment Polarity Protein 1
The DVL1 gene provides instructions for making a protein that plays a critical role in development before birth. It is one of three DVL genes in humans (DVL1, DVL2, and DVL3). The proteins produced from these genes work together in chemical signaling pathways known as Wnt signaling. These pathways control the activity of certain genes and regulate the interactions between cells during embryonic development. Signaling involving the DVL proteins appears to be important for the normal development of the brain, skeleton, and many other parts of the body.
At least 15 mutations in the DVL1 gene have been found to cause the autosomal dominant form of Robinow syndrome, a condition that affects the development of many parts of the body, particularly the skeleton. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. DVL1 gene mutations underlie a variant type of autosomal dominant Robinow syndrome called the osteosclerotic form, which features increased bone mineral density (osteosclerosis) affecting the bones of the skull.
All of the identified DVL1 gene mutations occur in a region of the gene known as exon 14. Each mutation is predicted to remove a segment of protein building blocks (amino acids) from the end of the DVL1 protein and add more than 100 new amino acids. Researchers are working to determine how these changes affect the protein's function. The changes may have a dominant-negative effect, which means that the altered protein produced from one copy of the DVL1 gene interferes with the function of the normal protein produced from the other copy of the gene. Alternately, the changes may have a gain-of-function effect, giving the altered protein a new, as-yet-undetermined function. Either way, the abnormal DVL1 protein likely impairs Wnt signaling. Problems with Wnt signaling pathways disrupt the development of many organs and tissues, leading to the features of Robinow syndrome. It is unclear how DVL1 gene mutations cause osteosclerosis in addition to the other signs and symptoms of the condition.
dishevelled 1 (homologous to Drosophila dsh)
dishevelled, dsh homolog 1
DSH homolog 1
segment polarity protein dishevelled homolog DVL-1