論文

査読有り 国際誌
2019年7月19日

Elucidation of the pathogenic mechanism and potential treatment strategy for a female patient with spastic paraplegia derived from a single-nucleotide deletion in PLP1

Journal of Human Genetics
  • Keiko Yamamoto-Shimojima
  • ,
  • Taichi Imaizumi
  • ,
  • Yusuke Aoki
  • ,
  • Ken Inoue
  • ,
  • Tadashi Kaname
  • ,
  • Yusuke Okuno
  • ,
  • Hideki Muramatsu
  • ,
  • Kohji Kato
  • ,
  • Toshiyuki Yamamoto

64
7
開始ページ
665
終了ページ
671
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s10038-019-0600-x
出版者・発行元
Springer Science and Business Media {LLC}

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder caused by abnormalities in the gene PLP1. Most females harboring heterozygous PLP1 abnormalities are basically asymptomatic. However, as a result of abnormal patterns of X-chromosome inactivation, it is possible for some female carriers to be symptomatic. Whole-exome sequencing of a female patient with unknown spastic paraplegia was performed to obtain a molecular diagnosis. As a result, a de novo heterozygous single-nucleotide deletion in PLP1 [NM_000533.5(PLP1_v001):c.783del; p.Thr262Leufs*20] was identified. RNA sequencing was performed in a patient-derived lymphoblastoid cell line, confirming mono-allelic expression of the mutated allele and abnormal inactivation of the wild-type allele. The patient-derived lymphoblastoid cell line was then treated with VX680 or 5azadC, which resulted in restored expression of the wild-type allele. These two agents thus have the potential to reverse inappropriately-skewed inactivation of the X-chromosome.

リンク情報
DOI
https://doi.org/10.1038/s10038-019-0600-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31004103
URL
http://orcid.org/0000-0002-9484-3505
ID情報
  • DOI : 10.1038/s10038-019-0600-x
  • ISSN : 1434-5161
  • ORCIDのPut Code : 56595737
  • PubMed ID : 31004103

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