Generation of Induced Pluripotent Stem Cells from a Female Patient with a Xq27.3-q28 Deletion to Establish Disease Models and Identify Therapies

Noriko Watanabe, Kohei Kitada, Katherine E. Santostefano, Airi Yokoyama, Sara M. Waldrop, Coy D. Heldermon, Daisuke Tachibana, Masayasu Koyama, Amy M. Meacham, Christina A. Pacak, Naohiro Terada

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Since it is extremely difficult to establish an animal model for human chromosomal abnormalities, induced pluripotent stem cells (iPSCs) provide a powerful alternative to study underlying mechanisms of these disorders and identify potential therapeutic interventions. In this study we established iPSCs from a young girl with a hemizygous deletion of Xq27.3-q28 who exhibited global developmental delay and intellectual disability from early in infancy. The deletion site on the X chromosome includes Fragile X Mental Retardation 1 (FMR1), the gene responsible for fragile X syndrome, which likely contributes to the patient's neurodevelopmental abnormalities. The FMR1 gene was expressed in approximately half of the iPSC clones we generated while it was absent in the other half due to the random inactivation of normal and abnormal X chromosomes. The normal or absent expression pattern of the FMR1 gene was not altered when the iPSCs were differentiated into neural progenitor cells (NPCs). Moreover, chromosome reactivating reagents such as 5-aza-2-deoxycytidine, trichostatin A, and UNC0638, were tested in an attempt to reactivate the suppressed FMR1 gene in affected iPSC-NPCs. The affected and control isogenic iPSCs developed in this study are ideal models with which to identify downstream consequences caused by the Xq27.3-q28 deletion and also to provide tools for high-throughput screening to identify compounds potentially improving the well-being of this patient population.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalCellular Reprogramming
Issue number4
StatePublished - Aug 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by National Institutes of Health (GM119977), the University of Florida Clinical and Translational Science Institute (UL1TR001427), and Xtraordinary Joy Foundation.

Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc.


  • chromosomal reactivation
  • induced pluripotent stem cells
  • intellectual disability
  • partial X chromosome deletion
  • X-linked disorders

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Generation of Induced Pluripotent Stem Cells from a Female Patient with a Xq27.3-q28 Deletion to Establish Disease Models and Identify Therapies'. Together they form a unique fingerprint.

Cite this