Ulcero-mutilating neuropathy in an Austrian kinship without linkage to hereditary motor and sensory neuropathy IIB and hereditary sensory neuropathy I loci

Objective: To elucidate genetic heterogeneity in ulcero-mutilating neuropat hy. Background: Ulcero-mutilating features and sensory loss have been obser ved in hereditary sensory neuropathy (HSN) and hereditary motor and sensory neuropathy (HMSN). HSN is characterized by marked distal sensory loss, fre quent toe and foot ulcerations, osteomyelitis, and necrosis, which may be c omplicated by toe or limb amputations. Motor and autonomic nerve involvemen t can also occur to a variable degree. Recently, autosomal-dominant HSN typ e I was mapped to chromosome 9q22 in four families. In two other families w ith ulcero-mutilating neuropathy, a gene locus was assigned to chromosome 3 q13-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 neurop athy, sensory loss, and amputations. Results: Linkage analysis with chromos omal markers representing the HSN I and HMSN IIB loci excluded these gene l oci in our family. Conclusions: These findings therefore indicate the exist ence of a third gene locus in autosomal-dominant inherited ulcero-mutilatin g neuropathies, showing that these neuropathies are genetically highly hete rogeneous.