WNK1/HSN2 founder mutation in patients with hereditary sensory and autonomic neuropathy: A Japanese cohort study

J. H. Yuan, A. Hashiguchi, A. Yoshimura, N. Sakai, M. P. Takahashi, T. Ueda, A. Taniguchi, S. Okamoto, N. Kanazawa, Y. Yamamoto, K. Saigoh, S. Kusunoki, M. Ando, Y. Hiramatsu, Y. Okamoto, H. Takashima

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9 Citations (Scopus)


The clinical and genetic spectrum of hereditary sensory and autonomic neuropathy (HSAN) is still unknown in Japan. We collected a broad cohort of 33 unrelated patients with predominant sensory and/or autonomic dysfunctions, who were referred to our genetic laboratory. A gene panel sequencing targeting 18 HSAN-related genes was performed using a next-generation sequencing system. A recurrent frame shift mutation in the WNK1/HSN2 gene, c.3237_3238insT (p.Asp1080*), was detected in 5 patients. This mutation was homozygous in 4 cases and of a compound heterozygous genotype in 1 case. Geographic and haplotype analysis of all 5 patients suggested a founder event. In addition, a novel heterozygous nonsense variant, c.2615C>G (p.Ser872*), was identified. All the 5 patients presented with severe sensory and autonomic dysfunctions at birth or during adolescence. In 2 patients, an uncommon phenotype of acute pathological pain presented at ~50 years of age. Here, we present the first founder mutation of WNK1/HSN2, in addition to French Canadian, which accounts for ~15.2% of Japanese patients with HSAN in our cohort. We have also reviewed all previously described mutations in WNK1/HSN2 and reconciled their nomenclature strategy on the basis of the current longest transcript.

Original languageEnglish
Pages (from-to)659-663
Number of pages5
JournalClinical Genetics
Issue number6
Publication statusPublished - 12-2017

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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