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The OTUD7A-Ankyrin pathway: a newly identified disease mechanism for the 15q13.3 microdeletion disorder

Molecular Psychiatry volume 28, pages 1400–1401 (2023)Cite this article

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No specific treatments are available for many neurodevelopmental disorders (NDDs), including the 15q13.3 microdeletions disorder, mostly due to unknown disease mechanisms. A recent study by Unda et al. [1] in Molecular Psychiatry reveals a new critical mechanism for neurodevelopment, which is impaired in the 15q13.3 microdeletion disorder.

Genomic copy number variations (CNVs) that involve deletions and/or duplications of segments of DNA are often associated with NDDs [2]. The 15q13.3 microdeletion disorder is a recurrent CNV with a highly heterogeneous range of clinical manifestations due to incomplete penetrance and expressivity, including intellectual disability (ID), autism spectrum disorder (ASD), epilepsy, and schizophrenia [3]. The 15q13.3 microdeletion contains several candidate protein-coding genes that potentially underly the clinical phenotype, including the Ovarian tumor domain containing protein 7 A (OTUD7A). Interestingly, a previous study using heterozygous 15q13.3 microdeletions and Otud7a knockout mouse models demonstrated that OTUD7A is critical for the regulation of cortical neuron dendritic and spine development [4]. However, the molecular mechanisms underlying the OTUD7A-driven neuronal abnormalities observed in the 15q13.3 microdeletion syndrome remained elusive.

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References

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Authors and Affiliations

  1. Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands

    Nicky Scheefhals, Ummi Ciptasari, Eline J. H. van Hugte & Nael Nadif Kasri

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  1. Nicky Scheefhals
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  2. Ummi Ciptasari
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  3. Eline J. H. van Hugte
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  4. Nael Nadif Kasri
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NS, UC, EJHvH and NNK wrote the manuscript and edited the manuscript.

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Correspondence to Nael Nadif Kasri.

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Scheefhals, N., Ciptasari, U., van Hugte, E.J.H. et al. The OTUD7A-Ankyrin pathway: a newly identified disease mechanism for the 15q13.3 microdeletion disorder. Mol Psychiatry 28, 1400–1401 (2023). https://doi.org/10.1038/s41380-023-01965-9

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