Cystic Fibrosis: Causes

Pathogenesis (development of disease)

Cystic fibrosis – cystic fibrosis (CF) – is an autosomal recessive inherited disease caused by the mutation (permanent genetic change) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (“cystic fibrosis transmembrane regulator”), a regulator protein of chloride transport, on the chromosome. In most cases, there is a deletion (loss) of three base pairs.

Mutation of the CFTR gene has various effects on water and electrolyte balance. The most important effect is an increase in the viscosity of the body secretions of the excretory glands due to a disturbance of the chloride channels.

Approximately 90% of affected individuals have exocrine pancreatic insufficiency (EPI; disease of the pancreas associated with insufficient production of digestive enzymes). Pancreatic fibrosis (connective tissue replacement of the perished glandular tissue of the pancreas) gradually causes degeneration of endocrine pancreatic function (in this case: Islets of Langerhans, which are primarily responsible for regulating serum glucose levels (blood sugar levels) – via the hormones insulin and glucagon) and thus loss of the ability to produce insulin. For early detection, this requires annual oral glucose tolerance tests from the age of 10.

Four forms of the mutation can be distinguished, with forms I to III suggesting more of a severe course.

Etiology (Causes)

Biographic causes

  • Genetic burden from parents, grandparents – Europeans and North Americans are most commonly affected at 1:3,000 live births
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism):
        • Genes: CFTR
        • SNP: rs113993960 in the CFTR (“cystic fibrosis transmembrane conductance regulator” gene) gene.
          • Allele constellation: DI (cystic fibrosis carrier).
          • Allele constellation: DD (causes cystic fibrosis).