Objective: To elucidate genetic heterogeneity in ulcero-mutilating neuropathy.

Background: Ulcero-mutilating features and sensory loss have been observed in hereditary sensory neuropathy (HSN) and hereditary motor and sensory neuropathy (HMSN). HSN is characterized by marked distal sensory loss, frequent toe and foot ulcerations, osteomyelitis, and necrosis, which may be complicated by toe or limb amputations. Motor and autonomic nerve involvement can also occur to a variable degree. Recently, autosomal-dominant HSN type I was mapped to chromosome 9q22 in four families. In two other families with ulcero-mutilating neuropathy, a gene locus was assigned to chromosome 3q13-q22. Because motor symptoms were prominent in these latter two kinships, the disease was designated HMSN type IIB or Charcot–Marie–Tooth type 2B (CMT2B) neuropathy.

Methods: We report detailed clinical, electrophysiologic, and genetic data on a large Austrian family with ulcero-mutilating neuropathy, sensory loss, and amputations.

Results: Linkage analysis with chromosomal markers representing the HSN I and HMSN IIB loci excluded these gene loci in our family.

Conclusions: These findings therefore indicate the existence of a third gene locus in autosomal-dominant inherited ulcero-mutilating neuropathies, showing that these neuropathies are genetically highly heterogeneous.