論文

査読有り 国際誌
2021年11月27日

Imaging-based evaluation of pathogenicity by novel DNM2 variants associated with centronuclear myopathy.

Human mutation
  • Kenshiro Fujise
  • ,
  • Mariko Okubo
  • ,
  • Tadashi Abe
  • ,
  • Hiroshi Yamada
  • ,
  • Kohji Takei
  • ,
  • Ichizo Nishino
  • ,
  • Tetsuya Takeda
  • ,
  • Satoru Noguchi

43
2
開始ページ
169
終了ページ
179
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/humu.24307

A centronuclear myopathy (CNM) is a group of inherited congenital diseases showing clinically progressive muscle weakness associated with the presence of centralized myonuclei, diagnosed by genetic testing and muscle biopsy. The gene encoding dynamin 2, DNM2, has been identified as a causative gene for an autosomal dominant form of CNM. However, the information of a DNM2 variant alone is not always sufficient to gain a definitive diagnosis as the pathogenicity of many gene variants is currently unknown. In this study, we identified five novel DNM2 variants in our cohort. To establish the pathogenicity of these variants without using clinicopathological information, we used a simple in cellulo imaging-based assay for T-tubule-like structures to provide quantitative data that enable objective determination of pathogenicity by novel DNM2 variants. With this assay, we demonstrated that the phenotypes induced by mutant dynamin 2 in cellulo are well correlated with biochemical gain-of-function features of mutant dynamin 2 as well as the clinicopathological phenotypes of each patient. Our approach of combining an in cellulo assay with clinical information of the patients also explains the course of a disease progression by the pathogenesis of each variant in DNM2-associated CNM.

リンク情報
DOI
https://doi.org/10.1002/humu.24307
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34837441
ID情報
  • DOI : 10.1002/humu.24307
  • PubMed ID : 34837441

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