What are the genetic changes related to keratoderma with woolly hair ?
Mutations in the JUP, DSP, DSC2, and KANK2 genes cause keratoderma with woolly hair types I through IV, respectively. The JUP, DSP, and DSC2 genes provide instructions for making components of specialized cell structures called desmosomes. Desmosomes are located in the membrane surrounding certain cells, including skin and heart muscle cells. Desmosomes help attach cells to one another, which provides strength and stability to tissues. They also play a role in signaling between cells.  Mutations in the JUP, DSP, or DSC2 gene alter the structure and impair the function of desmosomes. Abnormal or missing desmosomes prevent cells from sticking to one another effectively, which likely makes the hair, skin, 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. Some studies suggest that abnormal cell signaling may also contribute to cardiomyopathy in people with this group of conditions.  Unlike the other genes associated with keratoderma with woolly hair, the KANK2 gene provides instructions for making a protein that is not part of desmosomes. Instead, it regulates other proteins called steroid receptor coactivators (SRCs), whose function is to help turn on (activate) certain genes. SRCs play important roles in tissues throughout the body, including the skin. Studies suggest that mutations in the KANK2 gene disrupt the regulation of SRCs, which leads to abnormal gene activity. However, it is unclear how these changes underlie the skin and hair abnormalities in keratoderma with woolly hair type IV.