The N355K atlastin 1 mutation is associated with hereditary sensory neuropathy and pyramidal tract features

Mutations in atlastin-1 (ATL-1), a gene known to cause pure, early-onset autosomal dominant hereditary spastic paraplegia SPG3A, have been recently reported to cause hereditary sensory neuropathy I (HSN I). We describe the detailed clinical and electrophysiologic findings in the first family with ulcero-mutilating sensory neuropathy carrying the c. C1065A, p.N355K mutation in ATL-1.

Detailed clinical and electrophysiologic studies were performed in affected and at-risk family members. Motor and sensory nerve conductions studies (NCS) were carried out in upper and lower limbs. ATL-1 was screened for mutations by direct sequencing.

Ten patients were found to carry the N355K mutation. With the exception of the two youngest patients, all had trophic skin changes in the feet consisting mainly of painless ulcers. Frequently, amputation of toes, feet, or even more proximal parts of the lower legs became necessary. A variable degree of increased muscle tone was observed in younger patients, whilst some older affected individuals only presented with hyperreflexia of patellar tendon reflexes. NCS revealed signs of an axonal motor and sensory neuropathies.

Our family carrying the N355K ATL1 mutation, which was initially diagnosed as HSN I, enlarges the SPG3A phenotype. We therefore suggest that patients with HSN I excluded for more common causes of HSN I, and in particular, affected individuals who exhibit additional pyramidal tract features should also be screened for mutations in ATL1.