POGZ variants in neurodevelopmental disorders

Targeted gene(s)/phenotype under study :

  • POGO TRANSPOSABLE ELEMENT WITH ZNF DOMAIN; POGZ (OMIM: 614787)/WHITE-SUTTON SYNDROME; WHSUS (OMIM: 616364; ORPHA:468678)

Abstract :

Recently discovered, POGZ gene codes for a heterochromatin protein, playing as a transcriptional regulator involved in chromatin remodeling, neuronal proliferation and synaptic function.

Heterozygous pathogenic variants in POGZ, mostly occurring de novo, have been recently associated to neurodevelopmental disorders, intellectual disability, developmental delay with or without autism spectrum disorder (ASD) and White-Sutton Syndrome. To date, over 50 individuals with mutation in POGZ have been reported worldwide, mostly presenting truncating or splice-site pathogenetic variants.

POGZ knock-in mice exhibit abnormally elevated activation of excitatory neurons resulting in impaired neuronal development and altered behavioral performances, improved by the inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated synaptic transmission.

The aim of the study is to collect molecular and clinical data of POGZ-affected subjects in order to expande the knowledge of pathological mechanism and further investigate the already detected genotype-phenotype correlations in the light of proposing new therapeutic strategies.

Coordinating clinicians /researchers: 

  • Agnese Feresin
  • Maria Teresa Bonati

Institution :

Department of Genetics

Institute for Maternal and Child Health IRCCS Burlo Garofolo

Trieste, Italy

Contact : 

Specific Requirements beyond clinical data and genotype data sharing:

  • Re-analysis of DNA samples : Yes
  • Resampling of patients : Yes
  • Linked to a translational/basic research project? Potential study could be developed