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Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder
  1. Bruna Pereira Marquezini1,
  2. Mariana Moysés-Oliveira1,
  3. Anna Kloster1,
  4. Lais Cunha1,
  5. Tais Bassani Deconto1,
  6. Amanda Cristina Mosini1,
  7. Pedro Guerreiro1,
  8. Mayara Paschalidis1,
  9. Luana Nayara Gallego Adami1,
  10. Monica Levy Andersen1,2,
  11. Sergio Tufik1,2
  1. 1 Sleep Institute, Associação Fundo de Incentivo à Pesquisa, São Paulo, Brazil
  2. 2 Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil
  1. Correspondence to Dr Sergio Tufik, Sleep Institute, Associação Fundo de Incentivo à Pesquisa, Sao Paulo, SP, Brazil; Sergio.Tufik{at}unifesp.br

Abstract

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causative POGZ variants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among the POGZ regulatory targets, aiming to uncover the molecular pathways that, when disrupted by POGZ loss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect between POGZ targets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related to POGZ and its regulatory targets.

  • Sleep Wake Disorders
  • Mutation
  • Nervous System Diseases
  • Genetic Research

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Footnotes

  • BPM and MM-O contributed equally.

  • Contributors BPM and MM-O composed the gene lists. BPM, MM-O, AK, TBD, LC, MP, LNGA, PG and ACM performed data analysis. MLA and ST supervised and provided funding to the work. BPM and MM-O drafted the manuscript. All authors revised the manuscript.

  • Funding This work was supported by Associação Fundo de Incentivo à Pesquisa and grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (2020/13467-8—recipient: MLA, 2021/09089-0—recipient: MM-O) and Conselho Nacional de Desenvolvimento Científico e Tecnológico.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.