The DSC2 gene provides instructions for making a protein called desmocollin-2. This protein is found in many tissues, although it appears to be particularly important in the heart muscle and skin. Desmocollin-2 is a major component of specialized structures called desmosomes. These structures help hold neighboring cells together, which provides strength and stability to tissues. Desmosomes may also be involved in other critical cell functions, including chemical signaling pathways, the process by which cells mature to perform specific functions (differentiation), and the self-destruction of cells (apoptosis).
At least one mutation in the DSC2 gene has been found to cause a form of keratoderma with woolly hair classified as type III. It is characterized by thick, calloused skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); coarse, dry, fine, and tightly curled hair; and a potentially life-threatening form of heart disease called arrhythmogenic right ventricular cardiomyopathy (ARVC).
The known mutation, which is written as 1841delG, deletes one DNA building block (base pair) from the DSC2 gene. The resulting abnormal version of the desmocollin-2 protein alters the structure of desmosomes, preventing cells from attaching to one another effectively. Researchers suspect that the impaired connections between cells make the skin, hair, and heart muscle more fragile. Over time, as these tissues are exposed to mechanical stress (for example, friction on the surface of the skin or the constant contraction and relaxation of the heart muscle), they become damaged and can no longer function normally. This mechanism probably underlies the skin, hair, and heart problems that occur in keratoderma with woolly hair type III. Studies suggest that abnormal cell signaling may also contribute to cardiomyopathy in people with this condition.
Several other mutations in the DSC2 gene cause ARVC without palmoplantar keratoderma or woolly hair. It is unclear why some mutations in this gene affect the skin and hair, while others do not.
Genetics Home Reference provides information about arrhythmogenic right ventricular cardiomyopathy.
- cadherin family member 2
- desmocollin-2 isoform Dsc2a preproprotein
- desmocollin-2 isoform Dsc2b preproprotein
- desmosomal glycoprotein II/III