SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies

Abstract

Background: The variable clinical features of hereditary sensory and autonomic neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory neuropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be recognised as familial. Objective: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. Patients: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients with idiopathic sensory neuropathy were also screened for known mutations of these genes. Results: Of the 25 kindreds, only one had a mutation (SPTLC1 399T→G). This kindred, and 10 without identified mutations, had prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity with injuries but no weakness, one had restless legs and burning feet, and one had dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neuropathy. Conclusions: Adult onset HSAN I is clinically and genetically heterogeneous and further work is required to identify additional genetic causes. Known SPTLC1 or RAB7 mutations were not found in idiopathic sensory neuropathy.