POGLUT1

At least 11 mutations in the POGLUT1 gene have been found to cause Dowling-Degos disease. This condition results in various skin abnormalities, including a characteristic lacy pattern of abnormally dark skin coloring (hyperpigmentation) that occurs most often in the body's folds and creases.

Most of the POGLUT1 gene mutations that cause Dowling-Degos disease lead to an abnormally short protein with no function or change single protein building blocks (amino acids) resulting in a partial loss of protein function. As a result, protein O-glucosyltransferase 1 is less able or unable to add glucose molecules to Notch receptors. Without these sugar molecules, Notch receptors cannot bind to their ligands and the Notch pathway is halted. Because the varied functions of the Notch pathway affect many body systems and Dowling-Degos disease affects only the skin, it is unclear whether the signs and symptoms of this condition are due to impaired Notch signaling or disruption of an unknown function of protein O-glucosyltransferase 1 in melanocytes or other skin cells.

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