iPSC-derived neurons of CREBBP- and EP300-mutated Rubinstein-Taybi syndrome patients show morphological alterations and hypoexcitability

Valentina Alari, Silvia Russo, Benedetta Terragni, Paola Francesca Ajmone, Alessandra Sironi, Ilaria Catusi, Luciano Calzari, Daniela Concolino, Rosa Marotta, Donatella Milani, Daniela Giardino, Massimo Mantegazza, Cristina Gervasini, Palma Finelli, Lidia Larizza

Research output: Contribution to journalArticlepeer-review


Rubinstein-Taybi syndrome (RSTS) is a rare neurodevelopmental disorder characterized by distinctive facial features, growth retardation, broad thumbs and toes and mild to severe intellectual disability, caused by heterozygous mutations in either CREBBP or EP300 genes, encoding the homologous CBP and p300 lysine-acetyltransferases and transcriptional coactivators. No RSTS in vitro induced Pluripotent Stem Cell (iPSC)-neuronal model is available yet to achieve mechanistic insights on cognitive impairment of RSTS patients. We established iPSC-derived neurons (i-neurons) from peripheral blood cells of three CREBBP- and two EP300-mutated patients displaying different levels of intellectual disability, and four unaffected controls. Pan neuronal and cortical-specific markers were expressed by all patients’ i-neurons. Altered morphology of patients’ differentiating neurons, showing reduced branch length and increased branch number, and hypoexcitability of differentiated neurons emerged as potential disease biomarkers. Anomalous neuronal morphology and reduced excitability varied across different RSTS patients’ i-neurons. Further studies are needed to validate these markers and assess whether they reflect cognitive and behavioural impairment of the donor patients.

Original languageEnglish
Pages (from-to)130-140
Number of pages11
JournalStem Cell Research
Publication statusPublished - Jul 1 2018


  • Cognitive impairment
  • Disease-relevant cell phenotypes
  • iPSCs
  • Neuronal model
  • Rubinstein-Taybi syndrome

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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