De Novoarhgef9missense Variants Associated With Neurodevelopmental Disorder In Females: Expanding The Genotypic And Phenotypic Spectrum Ofarhgef9disease In Females

Individuals harboring pathogenic variants inARHGEF9, encoding an essential submembrane protein for gamma-aminobutyric acid (GABA)-ergic synapses named collybistin, show intellectual disability (ID), facial dysmorphism, behavioral disorders, and epilepsy. Only few affected females carrying large chromosomal rearrangements involvingARHGEF9have been reported so far. Through next-generation sequencing (NGS)-based panels, we identified two single nucleotide variants (SNVs) inARHGEF9in two females with neurodevelopmental features. Sanger sequencing revealed that these variants were de novo. The X-inactivation pattern in peripheral blood cells was random. We report the first affected females harboring de novo SNVs inARHGEF9, expanding the genotypic and phenotypic spectrum ofARHGEF9-related neurodevelopmental disorder in females.