Proximal dominant hereditary motor and sensory neuropathy with proximal dominance association with mutation in the TRK-fused gene

Sang Soo Lee, Hye Jin Lee, Jin Mo Park, Young Bin Hong, Kee Duk Park, Jeong Hyun Yoo, Heasoo Koo, Sung Chul Jung, Hyung Soon Park, Ji Hyun Lee, Min Goo Lee, Young Se Hyun, Khriezhanou Nakhro, Ki Wha Chung, Byung Ok Choi

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Importance: Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) has been reported as a rare type of autosomal dominant adult-onset Charcot-Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since 1997, and the causative gene has not been found. Objectives: To identify the genetic cause of HMSN-P in a Korean family and determine the pathogenic mechanism. Design: Genetic and observational analysis. Setting: Translational research center for rare neurologic disease. Participants: Twenty-eight individuals (12 men and 16 women) from a Korean family with HMSN-P. Main Outcome Measures: Whole-exome sequencing, linkage analysis, and magnetic resonance imaging . Results : Through whole-exome sequencing, we revealed that HMSN-P is caused by a mutation in the TRK-fused gene ( TFG ). Clinical heterogeneities were revealed in HMSN-P between Korean and Japanese patients. The patients in the present report showed faster progression of the disease compared with the Japanese patients, and sensory nerve action potentials of the sural nerve were lost in the early stages of the disease. Moreover, tremor and hyperlipidemia were frequently found. Magnetic resonance imaging of the lower extremity revealed a distinct proximal dominant and sequential pattern of muscular involvement with a clearly different pattern than patients with Charcot-Marie-Tooth disease type 1A. Particularly, endoneural blood vessels revealed marked narrowing of the lumen with swollen vesicular endothelial cells. Conclusions and Relevance: The underlying cause of HMSN-P proves to be a mutation in TFG that lies on chromosome 3q13.2. This disease is not limited to Japanese descendants, and marked narrowing of endoneural blood vessels was noted in the present study. We believe that TFG can affect the peripheral nerve tissue.

Original languageEnglish
Pages (from-to)607-615
Number of pages9
JournalJAMA Neurology
Issue number5
StatePublished - May 2013


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