Novel de Novo Nonsense Variants in AGO3 and KHSRP: Insights into Global Developmental Delay and Autism Spectrum Disorders through Whole Genome Analysis

Abstract

and bilateral optic nerve hypoplasia, Chiari malformation type I with normal myelinization. A comprehensive joint whole-genome analysis (WGS) of the proband and her unaffected parents was performed. The trio-WGS analysis identified novel de novo nonsense variants AGO3 : c.1324C>T (p.Gln442*) and KHSRP : c.1573C>T (p.Gln525*). These variants have not been reported in gnomAD and published literature. AGO3 and KHSRP are not currently associated with a known phenotype in the Online Mendelian Inheritance in Man (OMIM); however, they may be involved in neuronal development. Conclusions: This report highlights the utility of joint WGS analysis in identifying novel de novo genomic alterations in a patient with the spectrum of phenotypes of GDD and neurodevelopmental disorders. The role of these variants and genes in GDD requires further studies.