A novel RAB7 mutation associated with ulcero-mutilating neuropathy

There are two known autosomal dominant genes for the hereditary ulcero‐mutilating neuropathies: SPTLC1 (hereditary sensory neuropathy type 1) and RAB7 (Charcot–Marie–Tooth disease type 2B). We report a family with autosomal dominant ulcero‐mutilating neuropathy, developing in the teens and characterized by ulcers, amputations, sensory involvement in the feet but no motor features. Sequencing the RAB7 gene showed a novel heterozygous A to C mutation, changing asparagine to threonine at codon 161. The mutation is situated adjacent to a previously identified valine to methionine mutation at codon 162, implying a hotspot for mutations in the highly conserved C terminus of RAB7. Ann Neurol 2004;56:586–590