SCNN1B

At least 16 mutations in the SCNN1B gene can cause a condition known as Liddle syndrome. People with Liddle syndrome have high blood pressure (hypertension) and low levels of potassium in their blood (hypokalemia), often beginning in childhood. Mutations in the SCNN1B gene associated with Liddle syndrome lead to the production of an abnormally short beta subunit protein or result in the replacement of a single protein building block (amino acid) in the protein. These changes affect an important region of the protein involved in signaling for its breakdown (degradation). As a result of the mutations, the protein is not degraded, and more ENaC channels remain at the cell surface. The increase in channels at the cell surface abnormally increases the reabsorption of sodium (followed by water), which leads to hypertension. Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia.

Mutations in the SCNN1B gene have been identified in people with pseudohypoaldosteronism type 1 (PHA1). This condition typically begins in infancy and is characterized by low levels of sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood, and severe dehydration due to the loss of excess sodium and fluid in urine. In particular, SCNN1B gene mutations are involved in autosomal recessive PHA1, a severe form of the condition that does not improve with age.

Mutations in the SCNN1B gene that cause PHA1 often result in the replacement of a single amino acid in the beta subunit protein or lead to an abnormally short protein. These mutations result in reduced or absent ENaC channel activity. As a result, sodium reabsorption is impaired, leading to hyponatremia and other signs and symptoms of autosomal recessive PHA1. The reduced function of ENaC channels in lung epithelial cells leads to excess fluid in the lungs and recurrent lung infections.

Some people with cystic fibrosis-like syndrome have a mutation or a normal gene variation (polymorphism) in the SCNN1B gene. People with cystic fibrosis-like syndrome (also known as atypical cystic fibrosis or bronchiectasis with or without elevated sweat chloride type 1) have signs and symptoms that resemble those of cystic fibrosis, including breathing problems and lung infections. However, changes in the gene most commonly associated with cystic fibrosis, CFTR, cannot explain development of the condition. It is thought that a mutation or gene variation in the SCNN1B gene can disrupt sodium transport and fluid balance, which leads to the signs and symptoms of cystic fibrosis-like syndrome.