Severe congenital neutropenia (SCN) is a rare genetic disorder characterized by a significant decrease in the number of neutrophils, a type of white blood cell that plays a crucial role in fighting off bacterial infections. This condition is typically present at birth or becomes apparent within the first few weeks of life. SCN is caused by mutations in certain genes that are involved in the production and maturation of neutrophils.
ELANE gene mutations: The most common cause of SCN is mutations in the ELANE gene, which provides instructions for making an enzyme called neutrophil elastase. Neutrophil elastase is essential for the normal development and function of neutrophils. Mutations in the ELANE gene lead to the production of a defective enzyme, resulting in impaired neutrophil production and survival. These mutations are inherited in an autosomal dominant manner, meaning that a child has a 50% chance of inheriting the mutation if one parent carries it.
HAX1 gene mutations: Mutations in the HAX1 gene can also cause SCN. The HAX1 gene provides instructions for making a protein that is involved in the regulation of neutrophil development and survival. When HAX1 gene mutations occur, neutrophil production is disrupted, leading to SCN. These mutations can be inherited in an autosomal recessive manner, meaning that both parents must carry the mutation for a child to be affected.
G6PC3 gene mutations: Mutations in the G6PC3 gene can result in a form of SCN known as autosomal recessive congenital neutropenia (ARCN). The G6PC3 gene provides instructions for making an enzyme that is involved in glucose metabolism. Mutations in this gene disrupt neutrophil production and survival, leading to ARCN. Like HAX1 gene mutations, G6PC3 gene mutations are inherited in an autosomal recessive manner.
Other genetic mutations: In addition to mutations in the ELANE, HAX1, and G6PC3 genes, there are several other genetic mutations that have been associated with SCN. These include mutations in the GFI1, GFI1B, CSF3R, and WAS genes. Each of these mutations disrupts different aspects of neutrophil development and function, ultimately leading to SCN.
It is important to note that SCN is a genetic disorder and is not caused by environmental factors or lifestyle choices. While the specific genetic mutations responsible for SCN have been identified, the exact mechanisms by which these mutations lead to the development of the condition are still being studied. Researchers continue to investigate the underlying causes of SCN in order to develop more effective treatments and interventions for individuals affected by this rare disorder.