Background: The variable clinical features of hereditary sensory and autonomi c neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory ne uropathy could be caused by missense mutations of SPTLC1 a...Background: The variable clinical features of hereditary sensory and autonomi c neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory ne uropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be rec ognised 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 w ith idiopathic sensory neuropathy were also screened for known mutations of thes e genes. Results: Of the 25 kindreds, only one had a mutation (SPTLC1 399T→ G). This kindred, and 10 without identified mutations, had prominent mutilating foo t injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity w ith injuries but no weakness, one had restless legs and burning feet, and one ha d 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 neur opathy. Conclusions: Adult onset HSAN I is clinically and genetically heterogene ous and further work is required to identify additional genetic causes. Known SP TLC1 or RAB7 mutations were not found in idiopathic sensory neuropathy.展开更多
文摘Background: The variable clinical features of hereditary sensory and autonomi c neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory ne uropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be rec ognised 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 w ith idiopathic sensory neuropathy were also screened for known mutations of thes e genes. Results: Of the 25 kindreds, only one had a mutation (SPTLC1 399T→ G). This kindred, and 10 without identified mutations, had prominent mutilating foo t injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity w ith injuries but no weakness, one had restless legs and burning feet, and one ha d 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 neur opathy. Conclusions: Adult onset HSAN I is clinically and genetically heterogene ous and further work is required to identify additional genetic causes. Known SP TLC1 or RAB7 mutations were not found in idiopathic sensory neuropathy.
