In 1993, J. Takeda and colleagues identified the key gene responsible for PNH. The gene is called PIG-A. Most people with PNH have a genetic flaw or ‘mutation’ in the PIG-A gene, which affects how their red blood cells, white blood cells and platelets work.
Inside cells, DNA is organised into discrete sections called chromosomes. This study showed that the PIG-A gene is found on the X chromosome. This is one of the two human sex chromosomes (females have two X chromosomes, males have one X and one Y chromosome).
The PIG-A gene mutation is ‘somatic’ which means that it is not inherited, and instead, develops spontaneously in a person’s blood stem cells. Then, when those stem cells divide to make new cells, the mutation is passed on to them. This creates pools or ‘clones’ of mutated blood cells.
These mutated cells lack a key protein, known as a GPI anchor, which protects normal blood cells from being destroyed by the immune system. Without a GPI anchor, the mutated cells are attacked by part of the immune system, known as the complement system. This causes red blood cells to break down, leading to the symptoms of PNH. White blood cells become ‘sticky,’ increasing the risk of blood clots.
Now, over 20 years later, researchers realise that not everyone with PNH has a mutation in the PIG-A gene. PNH can be caused by mutations in other genes, found on different chromosomes. The PIG-T gene for example, which also helps to make GPI anchor proteins, is found on chromosome number 20.
Today, more than ten different genes have been found to play a role in PNH, and with each new piece of information that is discovered, researchers are learning more about PNH. This is important because it will help them to develop better diagnostics and new, improved treatments, that will, in turn, help patients.