title: Proximal dominant hereditary motor and sensory neuropathy with proximal dominance association with mutation in the TRK-fused gene.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  To identify the genetic cause of HMSN-P in a Korean family and determine the pathogenic mechanism.
  
  
  METHODS
  Genetic and observational analysis.
  
  
  METHODS
  Translational research center for rare neurologic disease.
  
  
  METHODS
  Twenty-eight individuals (12 men and 16 women) from a Korean family with HMSN-P.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Neurology, Chungbuk National University School of Medicine, Chungbuk, Korea.
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.forename: Kee-Duk
authors.initials: KD
authors.lastname: Park
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Yoo
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
authors.forename: Hyung Soon
authors.initials: HS
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.forename: Young Se
authors.initials: YS
authors.lastname: Hyun
authors.forename: Khriezhanou
authors.initials: K
authors.lastname: Nakhro
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
mesh_terms: D000328:Adult; D044466:Asian People; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D059472:Exome / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D015417:Hereditary Sensory and Motor Neuropathy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D011506:Proteins; C096163:TFG protein, human; D033921:Vesicular Transport Proteins