2.1. Paroxysmal nocturnal hemoglobinuria

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. In people with paroxysmal nocturnal hemoglobinuria, somatic mutations of the PIGA gene occur in blood-forming cells called hematopoietic stem cells. Hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting.

Individuals with paroxysmal nocturnal hemoglobinuria have one or more PIGA gene mutations in their hematopoietic stem cells, which leads to abnormal blood cells. As the abnormal hematopoietic stem cells multiply, populations of abnormal blood cells are formed, alongside normal blood cells produced by normal hematopoietic stem cells. The proportion of abnormal blood cells in the body affects the severity of the signs and symptoms of paroxysmal nocturnal hemoglobinuria.

Researchers have identified more than 100 somatic mutations in the PIGA gene. Some of these mutations alter the numbers or types of protein building blocks (amino acids) in phosphatidylinositol glycan class A, which impair its function. Other mutations result in the insertion of a premature stop signal in the instructions for making phosphatidylinositol glycan class A. As a result, an abnormally small protein, which is usually unstable, is produced.