Transcription Factor 4 and Myocyte Enhancer Factor 2C mutations are not common causes of Rett syndrome

Authors

  • Roksana Armani,

    1. NSW Centre for Rett Syndrome Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
    2. Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
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  • Hayley Archer,

    1. Institute of Medical Genetics, Cardiff University, University Hospital of Wales, Cardiff, UK
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  • Angus Clarke,

    1. Institute of Medical Genetics, Cardiff University, University Hospital of Wales, Cardiff, UK
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  • Pradeep Vasudevan,

    1. Leicester Royal Infirmary and University of Leicester, Leicester, England, UK
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  • Christiane Zweier,

    1. Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürmberg, Erlangen, Germany
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  • Gladys Ho,

    1. NSW Centre for Rett Syndrome Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
    2. Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
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  • Sarah Williamson,

    1. NSW Centre for Rett Syndrome Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
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  • Desiree Cloosterman,

    1. NSW Centre for Rett Syndrome Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
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  • Nan Yang,

    1. Institute for Neuroscience and Muscle Research, The Children's Hospital and Westmead, Sydney, NSW, Australia
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  • John Christodoulou

    Corresponding author
    1. NSW Centre for Rett Syndrome Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, NSW, Australia
    2. Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
    3. Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
    • Western Sydney Genetics Program, The Children's Hospital at Westmead, Locked Bag 4001, Westmead 2145, NSW, Australia.
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  • How to Cite this Article: Armani R, Archer H, Clarke A, Vasudevan P, Zweier C, Ho G, Williamson S, Cloosterman D, Yang N, Christodoulou J. 2012. Transcription Factor 4 and Myocyte Enhancer Factor 2C mutations are not common causes of Rett Syndrome. Am J Med Genet Part A 158A:713–719.

Abstract

The systematic screening of Rett syndrome (RTT) patients for pathogenetic sequence variations has focused on three genes that have been associated with RTT or related clinical phenotypes, namely MECP2, CDKL5, and FOXG1. More recently, it has been suggested that phenotypes associated with TCF4 and MEF2C mutations may represent a form of RTT.

Here we report on the screening of the TCF4 and MEF2C genes in a cohort of 81 classical, atypical, and incomplete atypical RTT patients harboring no known mutations in MECP2, CDKL5, and FOXG1 genes. No pathogenetic sequence variations were identified in the MEF2C gene in our cohort. However, a frameshift mutation in TCF4 was identified in a patient with a clinical diagnosis of “variant” RTT, in whom the clinical evolution later raised the possibility of Pitt–Hopkins syndrome. Although our results suggest that these genes are not commonly associated with RTT, we note the clinical similarity between RTT and Pitt–Hopkins syndrome, and suggest that RTT patients with no mutation identified in MECP2 be considered for molecular screening of the TCF4 gene. © 2012 Wiley Periodicals, Inc.

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