Rinsho Shinkeigaku (Clinical Neurology)

Symposium 3

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a mutation in TFG

Hiroyuki Ishiura, M.D. Ph.D.1) and Shoji Tsuji, M.D, Ph.D.1)

1)Department of Neurology, The University of Tokyo

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal dominant neurodegenerative disease characterized by proximal predominant weakness and muscle atrophy accompanied by distal sensory disturbance. Linkage analysis using 4 families identified a region on chromosome 3 showing a LOD score exceeding 4. Further refinement of candidate region was performed by haplotype analysis using high-density SNP data, resulting in a minimum candidate region spanning 3.3 Mb. Exome analysis of an HMSN-P patient revealed a mutation (c.854C>T, p.Pro285Leu) in TRK-fused gene (TFG). The identical mutation was found in the four families, which cosegregated with the disease. The mutation was neither found in Japanese control subjects nor public databases. Detailed haplotype analysis suggested two independent origins of the mutation. These findings indicate that the mutation in TFG causes HMSN-P.
Full Text of this Article in Japanese PDF (618K)

(CLINICA NEUROL, 53: 1203－1205, 2013)
key words: hereditary motor and sensory neuropathy with proximal dominant involvement, HMSN-P, exome analysis, haplotype analysis, TRK-fused gene (TFG)

(Received: 31-May-13)