ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor. Herein, we describe the clinical, neuroimaging, and molecular features of 28 individuals with ID and/or ASD due to de novo or inherited variants in the zinc finger protein 292 gene ( ZNF213). 1, 2, 3, 4 Such gene discovery efforts are important as the developmental roles of many of these pathways would not have otherwise been predicted from in vitro and model organism studies. Discovery of more than 1000 genes underlying ID and/or ASD to date has markedly informed the diagnosis for families with ID/ASD and has further led to the identification and characterization of multiple cellular pathways involved in human brain development, behavior, learning, and memory. As these genetic tools are becoming increasingly available in both the clinical diagnostic and research settings, a growing number of children with neurodevelopmental disorders (NDV) are now identified to have genetic variants that arise either de novo, or inherited as autosomal dominant, X-linked, or, less commonly, autosomal recessive traits. Knowledge about the genetic architecture of intellectual disability (ID), developmental delay (DD), and autism spectrum disorder (ASD) has increased dramatically over the past decade with the wide application of exome and genome sequencing (ES/GS) methods. Our results suggest that variants in ZNF292 are likely a recurrent cause of a neurodevelopmental disorder manifesting as ID with or without ASD. The clinical spectrum is broad, and most individuals present with mild to moderate ID with or without other syndromic features.
Conclusionĭe novo and dominantly inherited variants in ZNF292 are associated with a range of neurodevelopmental features including ID and ASD. ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor and is highly expressed in the developing human brain supporting its critical role in neurodevelopment. All ZNF292 variants were de novo, except in one family with dominant inheritance. Probands presented with ID as well as a spectrum of neurodevelopmental features including ASD, among others. Available data were analyzed to characterize the canonical phenotype and examine genotype–phenotype relationships. We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene ( ZNF292). Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. Genetics in Medicine volume 22, pages 538–546 ( 2020) Cite this article University of Washington Center for Mendelian Genomics (UW-CMG), &.De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder
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