論文

査読有り
2017年9月15日

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 B.V.

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 &gt
 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*5. Measurement of SPAST 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.

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
ID情報
  • DOI : 10.1016/j.jns.2017.07.011
  • ISSN : 1878-5883
  • ISSN : 0022-510X
  • PubMed ID : 28870597
  • SCOPUS ID : 85023632758

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