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Molecular Mechanisms of Childhood Overgrowth

Authors

  • KATRINA TATTON-BROWN,

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    • Dr. Kate Tatton-Brown is a Clinical Geneticist at the Institute of Cancer Research (ICR), St George's University of London and the Royal Marsden Hospital. She has a strong research interest and clinical experience in childhood overgrowth syndromes and has published widely on Sotos syndrome, the 15q overgrowth syndrome and, more recently, on Weaver syndrome.
  • ROSANNA WEKSBERG

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    • Dr. Rosanna Weksberg, MD, PhD, is a Professor of Pediatrics and Medical Genetics at the Hospital for Sick Children and the University of Toronto. Rosanna Weksberg has worked on human imprinting disorders and growth-related conditions since 1995, and has published extensively in this area. Dr. Weksberg's current research focuses on the epigenetic basis of normal human development and the identification of epigenetic alterations associated with human disease, especially in growth-related disorders. An important complementary research focus of the lab involves the characterization of the effects of both genetic variation and environmental exposures (including therapeutic agents) on epigenotype. Dr. Weksberg is funded by CIHR and NSERC. She is Associate Editor for the American Journal of Medical Genetics and an Editor for Frontiers in Epigenomics.

Correspondence to: Katrina Tatton-Brown, Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. E-mail: kate.tatton-brown@icr.ac.uk

Abstract

This issue of the Seminar Series C is dedicated to the molecular mechanisms of childhood overgrowth and celebrates the last decade of unprecedented gene discovery. Constitutional gene disorders, somatic gene disorders and imprinting dysregulation are each considered. The constitutional overgrowth genes discussed include NSD1, EZH2, GPC3, DIS3L2, and PTEN whilst the somatic overgrowth genes include AKT3, PIK3R2, and PIK3CA. Abnormalities of imprinting, exemplified by disruption of the (epi)genetic regulation of the imprinted 11p15 gene cluster, constitutes the final section of this issue. Many of the genes discussed in this issue encode components of the PI3K/mTOR growth regulatory pathway. This signaling cascade consists of dual, parallel branches, anchored by the serine–threonine kinase, mTOR, and has diverse downstream effects including inhibition of apoptosis, activation of protein synthesis, and enhanced cell survival. Activation of the PI3K/mTOR pathway promotes growth whereas inhibition, or abrogation, results in decreased cellular growth. Despite the rapid advances of the last decade, there is still an enormous amount to discover. We hope that some of the work reviewed in this issue will facilitate the next decade's discoveries and we look forward to a 10 years as productive as the last. © 2013 Wiley Periodicals, Inc.

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