Zeynep Tümer

Abstract PACS1-related disorder (PACS1-RD), also known as Schuurs-Hoeijmakers syndrome, is a rare autosomal dominant neurodevelopmental disorder predominantly caused by the recurrent de novo c.607 C > T p.(Arg203Trp) gain-of-function variant. Although core clinical features have been delineated, systematic data on developmental milestones, growth parameters, and clinical variability remain limited.

Abstract Biallelic inactivating variants in ZNF142 underlie a clinically variable neurodevelopmental disorder. ZNF142 is a zinc-finger transcription factor with potential roles on chromatin organization, implying a possible association of ZNF142 loss of function with perturbed genome-wide DNA methylation (DNAm) pattern.

1 Introduction Approximately one-third of monogenic disorders are caused by nonsense or frameshift variants that generate premature termination codons (PTC), most of which are subsequently degraded by nonsense-mediated mRNA decay (NMD) [1]. The Up-frameshift (UPF) protein family plays a critical role in NMD and includes UPF1, UPF2, and UPF3A/UPF3B, each contributing uniquely to NMD and working synergistically to ensure the fidelity of gene expression [2].