Gene/phenotype/disorder of interest
YWHAZ (OMIM *601288)
Abstract
Heterozygous missense and truncating variants in YWHAZ, encoding 14-3-3z, have recently been reported as de novo events in a few individuals with isolated or syndromic neurodevelopmental phenotypes. The clinical spectrum is broad and multisystem, encompassing global developmental delay/intellectual disability, epilepsy, brain malformations, reduced growth and dysmorphic features. Notably, one missense variant has been associated with cardiofaciocutaneous syndrome, a RASopathy known to result from GoF variants in BRAF, MAP2K1, and MAP2K2, resulting in increased MAPK signalling.
We are currently assembling a large cohort of affected individuals to further delineate the phenotypic spectrum and heterogeneity associated with pathogenic YWHAZ variants and to identify clinically relevant genotype-phenotype correlations. Complementary in silico, in vitro, and in vivo approaches are ongoing to investigate the molecular mechanisms underlying disease and validate the clinical relevance of VUS involving this gene.
Coordinating clinician
Marco Tartaglia; marco.tartaglia@opbg.net
Institution
Molecular Genetics and Functional Genomics, Bambino Gesù Children’s Hospital IRCCS, Rome
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples: N
- Resampling of patients: Y/N
- Linked to a translational/basic research project? Y