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Presence of colocalised phosphorylated TDP-43 and TFG proteins in the frontotemporal lobes of HMSN-P
  1. Kengo Maeda1,
  2. Ryo Idehara1,
  3. Ken-ichi Mukaisho2
  1. 1 Department of Neurology, National Hospital Organisation Higashiomi General Medical Center, Higashi-ohmi, Japan
  2. 2 Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan
  1. Correspondence to Dr Kengo Maeda, Department of Neurology, Vories Memorial Hospital, Omi-hachiman 523-8523, Japan; maeda{at}

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Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) was originally reported in the Okinawa1 and Shiga2 prefectures of Japan. Some families carrying the disease immigrated abroad to countries such as Brazil.3 The causative gene has been identified as the TRK-fused gene (TFG).4 TFG is localised to the endoplasmic reticulum exit sites and plays an important role in protein secretion.4 HMSN-P is inherited in an autosomal dominant manner. Its symptoms include weakness and atrophy of the limb, which start from the proximal muscles. Muscle atrophy expands to the tongue and respiratory muscles, and patients develop bulbar palsy and respiratory failure. Additionally, they do not usually develop pyramidal tract signs, and sensory symptoms are minimal. The natural course lasts approximately 20 years or longer. There is only one single case report in which immunohistochemistry using anti-TFG antibody was performed.4 According to that report, cytoplasmic inclusion containing TFG was found in neurons of the precentral gyrus, spinal anterior horn and dorsal root ganglion (DRG). We present the case of a patient with HMSN-P who died of respiratory failure within 4 years after onset. Part of his clinical course has been described previously.5 We herein report the findings of his pathological examination.

Case report

A 38-year-old man presented with weakness in his left upper limbs. He worked as a course maintainer in a golf field. His mother, who had the same symptoms, developed to respiratory failure and died in her 40s. His maternal uncle also had the same disease. He was case V-4 of Family 2 described in Ishiura et al’s report.4 Patients with HMSN-P in his family, including him, had a heterozygous missense mutation, c.854C>T (p.Pro285Leu), in TFG. His external ocular movement was normal. There was neither facial weakness nor bulbar palsy. The …

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  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Shiga University of Medical Science Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.