Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder

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Marquezini, Bruna Pereira ; Moyses-Oliveira, Mariana ; Kloster, Anna ; Cunha, Lais ; Deconto, Tais Bassani ; Mosini, Amanda Cristina ; Guerreiro, Pedro ; Paschalidis, Mayara ; Adami, Luana Nayara Gallego ; Andersen, Monica Levy ; Tufik, Sergio

• Document type: Journal article
• Source: JOURNAL OF MEDICAL GENETICS; v. 61, n. 6, p. 4-pg., 2024-02-13.

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. (AU)

• FAPESP's process: 21/09089-0 - High throughput genomic edition to investigate neurodevelopmental disorders using isogenic cellular models
• Grantee: Mariana Moysés Oliveira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/13467-8 - The relationship between obstructive sleep apnea and its comorbidities with the intestinal microbiome: interface with sexuality and reproductive function
• Grantee: Monica Levy Andersen
• Support Opportunities: Research Projects - Thematic Grants