Cole, disease ... (Cole disease) - Gen ENPP1.
Cole's disease is a disorder that affects the skin. Usually, people affected have hypopigmentation in the arms and legs and punctate palmoplantar keratoderma. These characteristics of the skin are present at birth or develop in the first year of life. In some cases, individuals with disease Cole develop calcifications in tendons, which can cause pain during movement. These calcifications can also develop in the skin or breast tissue.
This process is due to mutations in the ENPP1 gene, located on the long arm of chromosome 6 (6q22-q23). This gene encodes a protein that helps prevent minerals, including calcium, deposited in the tissues of the body where not correspond. Also it plays a role in the control of cell signaling in response to the hormone insulin, through the interaction between a part of the protein ENPP1 SMB2 called the domain and the insulin receptor. Insulin plays many roles in the body, including the regulation of sugar levels in the blood by controlling the amount of glucose passing blood cells to be used as energy. Cell signaling in response to insulin, is also important for the maintenance of the epidermis, as it helps control the transport of pigment melanin from melanocytes to keratinocytes, and is also involved in the development of keratinocytes.
They have identified at least 3 ENPP1 gene mutations in people with Cole disease. These mutations change the domain structure SMB2, disrupting its interaction with the insulin receptor and affects cellular signaling. Consequent deterioration of the function of ENPP1 melanin transport and the development of keratinocytes leads to hypopigmentation and keratoderma that occurs in the disease Cole. Mutations can also endanger control of calcification by ENPP1, which probably explains the abnormal calcium deposits that occur in some people with the disease. For reasons that are unclear, changes in insulin signaling not seem to affect control of blood sugar.
Cole's disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. In most cases of this disease, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with disease Cole, by complete PCR amplification of the exons of the ENPP1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).