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Author Notes:

Corresponding author: Andrew R. Mitz, arm@nih.gov

We thank Per Qvist for help with the BRD1 and ZBED4 gene reviews.

We thank Drs J Giza, C Sala, C Verpelli, and YH Jiang for their comments on an early draft of the manuscript.

Conflict of interest: The authors declare that they have no conflict of interest.

Subjects:

Research Funding:

This research was supported (in part) by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (Annual Report numbers: ZIA MH002868 and ZIAMH002886), by a Seed Grant from the Simons Center for the Social Brain, at the Genes of Phelan McDermid syndrome 299 Massachusetts Institute of Technology, and support from the Simons Foundation to WEK, and by the Slifka/Ritvo Innovation in Autism Award and Whitehall (2015-08-86), Brain Research Foundation (BRFSG-2016-08) and Brain and Behaviour Foundation (25456) Grants to AS.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Genetics & Heredity
  • AUTISM SPECTRUM DISORDER
  • ACTIVATED PROTEIN-KINASE
  • DELETION SYNDROME
  • SCAFFOLD PROTEINS
  • SHANK3 GENE
  • CONTROLLED-TRIAL
  • BRAIN
  • SCHIZOPHRENIA
  • CEREBELLAR
  • EXPRESSION

Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome

Journal Title:

European Journal of Human Genetics

Volume:

Volume 26, Number 3

Publisher:

, Pages 293-302

Type of Work:

Article | Final Publisher PDF

Abstract:

Chromosome 22q13.3 deletion (Phelan McDermid) syndrome (PMS) is a rare genetic neurodevelopmental disorder resulting from deletions or other genetic variants on distal 22q. Pathological variants of the SHANK3 gene have been identified, but terminal chromosomal deletions including SHANK3 are most common. Terminal deletions disrupt up to 108 protein-coding genes. The impact of these losses is highly variable and includes both significantly impairing neurodevelopmental and somatic manifestations. The current review combines two metrics, prevalence of gene loss and predicted loss pathogenicity, to identify likely contributors to phenotypic expression. These genes are grouped according to function as follows: molecular signaling at glutamate synapses, phenotypes involving neuropsychiatric disorders, involvement in multicellular organization, cerebellar development and functioning, and mitochondrial. The likely most impactful genes are reviewed to provide information for future clinical and translational investigations.

Copyright information:

© 2018 The author.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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