Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders

Michela Fagiolini; Annarita Patrizi; Jocelyn LeBlanc; Lee-Way Jin; Izumi Maezawa; Sarah Sinnett; Steven J Gray; Sophie Molholm; John J Foxe; Michael V Johnston; Sakkubai Naidu; Mary Blue; Ahamed Hossain; Shilpa Kadam; Xinyu Zhao; Quiang Chang; Zhaolan Zhou; Huda Zoghbi

doi:10.1016/j.neuroscience.2020.04.037

Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders

Neuroscience. 2020 Oct 1:445:190-206. doi: 10.1016/j.neuroscience.2020.04.037. Epub 2020 Apr 29.

Authors

Michela Fagiolini¹, Annarita Patrizi², Jocelyn LeBlanc², Lee-Way Jin³, Izumi Maezawa³, Sarah Sinnett⁴, Steven J Gray⁴, Sophie Molholm⁵, John J Foxe⁶, Michael V Johnston⁷, Sakkubai Naidu⁷, Mary Blue⁷, Ahamed Hossain⁷, Shilpa Kadam⁷, Xinyu Zhao⁸, Quiang Chang⁸, Zhaolan Zhou⁹, Huda Zoghbi¹⁰

Affiliations

¹ Children's Hospital Intellectual and Developmental Disabilities Research Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: michela.fagiolini@childrens.harvard.edu.
² Children's Hospital Intellectual and Developmental Disabilities Research Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
³ UC Davis MIND Institute, University of California, Sacramento, CA, USA.
⁴ UNC Intellectual and Developmental Disabilities Research Center, University of North Carolina, Gene Therapy Center and Dept. of Ophthalmology, Chapel Hill, NC, USA; Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.
⁵ The Cognitive Neurophysiology Laboratory, Departments of Pediatrics, Neuroscience, and Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA.
⁶ The Cognitive Neurophysiology Laboratory, Ernest J. Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
⁷ Kennedy Krieger Institute Intellectual and Developmental Disabilities Research Center/Hugo Moser Research Institute at Kennedy Krieger and Johns Hopkins School of Medicine, USA.
⁸ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Department of Genetic, Epigenetic Institute, University of Pennsylvania Perelman School of Medicine, Intellectual and Developmental Disabilities Research Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
¹⁰ Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, USA.

Abstract

Disruptions in the gene encoding methyl-CpG binding protein 2 (MECP2) underlie complex neurodevelopmental disorders including Rett Syndrome (RTT), MECP2 duplication disorder, intellectual disabilities, and autism. Significant progress has been made on the molecular and cellular basis of MECP2-related disorders providing a new framework for understanding how altered epigenetic landscape can derail the formation and refinement of neuronal circuits in early postnatal life and proper neurological function. This review will summarize selected major findings from the past years and particularly highlight the integrated and multidisciplinary work done at eight NIH-funded Intellectual and Developmental Disabilities Research Centers (IDDRC) across the US. Finally, we will outline a path forward with identification of reliable biomarkers and outcome measures, longitudinal preclinical and clinical studies, reproducibility of results across centers as a synergistic effort to decode and treat the pathogenesis of the complex MeCP2 disorders.

Keywords: animal models; biomarkers; neurodevelopmental disorders; signaling pathways; translational.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Carrier Proteins
Child
Developmental Disabilities
Humans
Methyl-CpG-Binding Protein 2* / genetics
Methyl-CpG-Binding Protein 2* / metabolism
Mutation
Reproducibility of Results
Rett Syndrome* / genetics

Substances

Carrier Proteins
MECP2 protein, human
Methyl-CpG-Binding Protein 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding