TDRKH is a candidate gene for an autosomal dominant distal hereditary motor neuropathy

Shiroh Miura, Kengo Kosaka, Takuo Nomura, Shuji Nagata, Tomofumi Shimojo, Takuya Morikawa, Ryuta Fujioka, Masaya Harada, Takayuki Taniwaki, Hiroki Shibata

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Distal hereditary motor neuropathies (dHMNs) comprise a group of clinically and genetically heterogeneous inherited lower motor neuron syndromes mainly characterized by a distal-predominant pattern of progressive muscle atrophy, weakness and hyporeflexia, without sensory dysfunction. Although at least 21 causative genes for dHMN have been reported, mutational scanning of these genes often fails to identify the causative variants in dHMN cohorts, suggesting that additional causative genes remain to be identified. We studied a four-generation pedigree of a Japanese family with autosomal dominant dHMN to provide insight into the pathogenetic basis of the disease. Neurological examinations were performed on all six family members enrolled in this study. Whole-exome sequencing (WES) was used to identify the causative gene for dHMN. The clinical features of the patients included muscle weakness with distal extensor dominancy in the lower extremities, accompanied by facial and neck flexor muscle impairment, no sensory involvement, and areflexia. Nerve conduction studies demonstrated axonal changes mainly in the peroneal nerve. WES combined with rigorous filtering revealed three missense variants (NM_001083964: c.851G > A [p.Arg284His] in TDRKH, NM_002858: c.1654G > T [p.Gly552Cys] in ABCD3, NM_001005164: c.898A > T [p.Ile300Phe], in OR52E2). The variant in TDRKH is located in a conserved region of the tudor domain which is also present in the survival of motor neuron (SMN) protein, encoded by the SMN1 gene. Therefore, we concluded the variant in TDRKH is likely to be responsible for dHMN in our pedigree.

本文言語英語
論文番号103594
ジャーナルEuropean Journal of Medical Genetics
62
12
DOI
出版ステータス出版済み - 12月 2019

!!!All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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