RETREG1

Hereditary sensory and autonomic neuropathy type II

Mutations in the RETREG1 gene are responsible for one type of hereditary sensory and autonomic neuropathy type II (HSAN2) called HSAN2B; at least five mutations have been identified in affected individuals. People with HSAN2B lose the ability to feel pain or sense hot and cold. The RETREG1 gene mutations may lead to an abnormally short and nonfunctional protein. The resulting lack of functioning RETREG1 protein impairs autophagy of the endoplasmic reticulum and alters the structure of the Golgi apparatus in sensory and autonomic neurons.

Researchers suspect that an inability to break down parts of the endoplasmic reticulum when they are no longer needed, and the subsequent accumulation of these structures and other proteins in cells, leads to cell death. The loss of sensory and autonomic neurons due to impaired autophagy results in the signs and symptoms of HSAN2B. It is unclear what role abnormalities of the Golgi apparatus play in the condition.