論文

査読有り
2017年9月

Spastic paraplegia type 4: A novel SPAST splice site donor mutation and expansion of the phenotype variability

JOURNAL OF THE NEUROLOGICAL SCIENCES
  • Toshitaka Kawarai
  • ,
  • Celeste Montecchiani
  • ,
  • Ryosuke Miyamoto
  • ,
  • Fabrizio Gaudiello
  • ,
  • Carlo Caltagirone
  • ,
  • Yuishin Izumi
  • ,
  • Ryuji Kaji
  • ,
  • Antonio Orlacchio

380
開始ページ
92
終了ページ
97
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jns.2017.07.011
出版者・発行元
ELSEVIER SCIENCE BV

Mutations in SPG4/SPAST are the most frequent molecular aetiology in the autosomal dominant form of hereditary spastic paraplegia (HSP). Loss-of-function and haploinsufficiency in SPAST have been demonstrated and the pure form of spastic paraplegia is a main clinical manifestation. This study is to explore the novel SPAST splice site donor variant, c.1004 + 3A> C, in seven patients from two families, one from Italy and the other from Japan. Exon 6 is skipped out by the variant, leading to a premature termination of translation, p.Gly290Trpfs*S. Measurement of SPAS7 transcripts in lymphocytes demonstrated a reduction through nonsense-mediated mRNA decay (NMD). Intra- and inter-familial phenotypic variations were observed, including age-at-onset, severity of spasticity, and scoliosis. Our study demonstrated further evidence of allelic heterogeneity in SPG4, dosage effects through NMD, and broad clinical features of the SPAST mutation. (C) 2017 Elsevier B.V. All rights reserved.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1016/j.jns.2017.07.011
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28870597
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000412033400021&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.jns.2017.07.011
  • ISSN : 0022-510X
  • eISSN : 1878-5883
  • PubMed ID : 28870597
  • Web of Science ID : WOS:000412033400021

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