Neurogenetics

, Volume 7, Issue 3, pp 175–183

Molecular mechanism of rigid spine with muscular dystrophy type 1 caused by novel mutations of selenoprotein N gene

Authors

  • Yuji Okamoto
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
    • Department of Molecular Pathology, Center for Chronic Vial DiseaseKagoshima University School of Medicine
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Itsuro Higuchi
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Wataru Matsuyama
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Masahito Suehara
    • Department of NeurologyOkinawa Hospital
  • Yasushi Nishihira
    • Department of NeurologyOkinawa Hospital
  • Akihiro Hashiguchi
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Ryuki Hirano
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Arlene R. Ng
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Masanori Nakagawa
    • Department of Neurology and GerontologyKyoto Prefectural University of Medicine
  • Shuji Izumo
    • Department of Molecular Pathology, Center for Chronic Vial DiseaseKagoshima University School of Medicine
  • Mitsuhiro Osame
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
  • Kimiyoshi Arimura
    • Department of Neurology and GeriatricsKagoshima University, Graduate School of Medical and Dental Sciences
Original Article

DOI: 10.1007/s10048-006-0046-0

Cite this article as:
Okamoto, Y., Takashima, H., Higuchi, I. et al. Neurogenetics (2006) 7: 175. doi:10.1007/s10048-006-0046-0

Abstract

Mutations of selenoprotein N, 1 gene (SEPN1) cause rigid spine with muscular dystrophy type 1 (RSMD1), multiminicore disease, and desmin-related myopathy. We found two novel SEPN1 mutations in two Japanese patients with RSMD1. To clarify the pathomechanism of RSMD1, we performed immunohistochemical studies using a newly developed antibody for selenoprotein N. Selenoprotein N was diffusely distributed in the cytoplasm of the control muscle, but was reduced and irregularly expressed in the cytoplasm of a patient with RSMD1. The expression pattern was very similar to that of calnexin, a transmembrane protein of the endoplasmic reticulum. Selenoprotein N seems to be an endoplasmic reticulum glycoprotein, and loss of this protein leads to disturbance of muscular function. One of the families had the SEPN1 homozygous mutation in the initiation codon 1_2 ins T in exon 1 and showed truncated protein expression. The other had a homozygous 20-base duplication mutation at 80 (80_99dup, frameshift at R27) which, in theory, should generate many nonsense mutations including TGA. These nonsense mutations are premature translation termination codons and they degrade immediately by the process of nonsense-mediated decay (NMD). However, truncated selenoprotein N was also expressed. A possible mechanism behind this observation is that SEPN1 mRNAs may be resistant to NMD. We report on the possible molecular mechanism behind these mutations in SEPN1. Our study clarifies molecular mechanisms of this muscular disorder.

Keywords

SEPN1Rigid spine syndromeAnti-selenoprotein N antibodyRSMD1SEPN-RM

Copyright information

© Springer-Verlag 2006