The ATP1A1-related disorders are caused by a mutation in the ATP1A1 gene. A gene is a carrier of hereditary information. All genes together are responsible for the function and appearance of the body. A gene is made by different letters, like a word. Each gene undergoes biologics processes that lead to formation of a specific protein, which has specific biological functions inside the human cells and body. A mutation consists in a change of one of these letters, thus making the word incorrect. Consequently, the mutated gene alters the protein formation and this might lead to disease.
ATP1A1 encodes the α1 isoform of the Na+, K+-ATPase, a protein responsible for active transport of three sodium ions (out) and two potassium ions (in) across the plasma membrane, powered by the hydrolysis of ATP. This ion pump maintains the electrochemical cellular gradient, which is essential for functions such as osmoregulation, ion transport, and electrical excitability of nerve and muscle. The Na+, K+-ATPase is a heterodimer composed by α and β subunits. The catalytic α subunit binds the two ions as well as ATP. Four α isoforms are encoded by four distinct genes (ATP1A1-4). ATP1A1 is expressed in most tissues, particularly in kidneys and the nervous system.
The ATP1A1-related disorders are autosomal dominant diseases. This means that one mutated copy (of the two copies) of the ATP1A1 gene is required to develop the disease. When an individual has a mutation in ATP1A1, it can be arisen de novo (i.e., newly arisen) or it can be inherited from a parent. Each individual with a mutation in ATP1A1 has a 50% chance to transmit the disease to the child, regardless of the sex of the child (i.e., man and woman are equally likely to have these mutations and sons and daughter are equally likely to inherit them). This is called autosomal dominant inheritance.
ATP1A1