Peripheral neuropathy: why only some mutations cause disease

Inherited peripheral neuropathies (IPN) are cruel genetic diseases that affect around 1 in 2,500 individuals. A person affected by IPN develops high foot arches, curled toes, thin calves, and walks awkwardly or trips. Their fingers may become clawed and, because they lose sensation, they may not notice minor injuries. In some cases, the weakness of the muscles supporting the torso can lead to a curved spine.

Mutations in more than 100 genes can cause IPN, including in seven of the 37 genes that code for enzymes called aminoacyl-tRNA synthetases (ARS). However, only some mutations in the ARS genes result in peripheral neuropathy. Others do not.