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Neurogenetic Aspects of Hyperphosphatasia in Mabry Syndrome

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Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP)

Part of the book series: Subcellular Biochemistry ((SCBI,volume 76))

Abstract

An autosomal recessive syndrome of hyperphosphatasia (elevated circulating alkaline phosphatase (AP), seizures and neurologic deficits) was first described by Mabry and colleagues in 1970. Over the ensuing four decades, few cases were reported. In 2010, however, new families were identified and the syndromic nature of the disorder confirmed. Shortly thereafter, next generation sequencing was used to characterize causative defects in the glycosyl phosphatidylinositol (GPI) biosynthetic pathway, based partly on our understanding of how AP is anchored by GPI to the plasma membrane. Whether the seizures and cognitive defects seen in Mabry syndrome patients are attributable in part to the constant hyperphosphatasia is not known, as there are more than 250 other proteins dependent on GPI for their anchoring to the plasma membrane . However, Mabry syndrome may provide a new window on AP function in growth and development.

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Acknowledgements

We thank Drs. A.Y. Shuen and A. Gozdzik for critical review of the manuscript, and we acknowledge the enthusiastic support proffered by Professors M.P. Whyte and M Michael Cohen Jr. for the very first studies of this condition two decades ago. We also thank the affected families and numerous colleagues around the world for their various contributions.

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    David E. C. Cole & Miles D. Thompson

  2. Department of Clinical Pathology, Sunnybrook Health Sciences Center, Toronto, ON, Canada

    David E. C. Cole

Authors
  1. David E. C. Cole
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  2. Miles D. Thompson
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Correspondence to David E. C. Cole .

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Editors and Affiliations

  1. National Centre for Scientific Research (CNRS), University of Toulouse-UPS, Toulouse, France

    Caroline Fonta

  2. Wigner Research Centre for Physics, Hungarian Academy of Sciences, Budapest, Hungary

    László Négyessy

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Cole, D.E.C., Thompson, M.D. (2015). Neurogenetic Aspects of Hyperphosphatasia in Mabry Syndrome. In: Fonta, C., Négyessy, L. (eds) Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP). Subcellular Biochemistry, vol 76. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7197-9_16

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