SLC12A6-related disorders can be inherited in an autosomal recessive and autosomal dominant manner.
The autosomal recessive disorder (HMSN/ACC or Andermann syndrome) develops when both copies of the gene (from the mother and from the father) have a defective change. Most changes that were associated with the autosomal recessive disorder were predicted loss-of-function mutations. These include nonsense, frameshift and essential splice changes. Some missense changes have been reported to cause HMSN/ACC as well. Carriers of these defective changes, affecting only one of the two copies of the gene, did not show any relevant symptoms.
For the autosomal dominant disorder, only one of the two copies of the gene need to have a defective change. In most cases, the mutations occurred de novo which means that the affected individuals had sporadic mutations that was not present in the healthy parents. It can also be inherited from an affected parent. So far, only few missense changes have been reported to cause the autosomal dominant disorder. The exact pathomechanism is yet unclear.
SLC12A6