Identification of a de novo FOXP1 mutation and incidental discovery of inherited genetic variants contributing to a case of autism spectrum disorder and epilepsy

Abstract

Background Autism spectrum disorder is commonly co‐diagnosed intellectual disability, language disorder, anxiety, and epilepsy, however, symptom management is difficult due to the complex genetic nature of ASD. Methods We present a next‐generation sequencing‐based case study with both de novo and inherited genetic variants and highlight the impact of structural variants on post‐translational regulation of protein expression. Since management of symptoms has classically been through pharmaceutical therapies, a pharmacogenomics screen was also utilized to determine possible drug/gene interactions. Results A de novo variant was identified within the FOXP1 3′ untranslated regulatory region using exome sequencing. Additionally, inherited variants that likely contribute to the current and potential future traits were identified within the COMT, SLC6A4 , CYP2C19, and CYP2D6 genes. Conclusion This study aims to elucidate how a collection of variant genotypes could potentially impact neural development resulting in a unique phenotype including ASD and epilepsy. Each gene's contribution to neural development is assessed, and the interplay of these genotypes is discussed. The results highlight the utility of exome sequencing in conjunction with pharmacogenomics screening when evaluating possible causes of and therapeutic treatments for ASD‐related symptoms.

CircRNA‐associated ceRNA regulatory networks as emerging mechanisms governing the development and biophysiopathology of epilepsy

“…64 Epilepsy and autism spectrum diseases may result from a genetic variation-related de novo FOXP1 mutation. 65 The circ ANKMY2/miR106b-5p axis was found to be able to influence FOXP1 expression in this study. Additionally, the inhibition of FOXP1 restored the impacts of miR-106b-5p repression on the growth, formation of colonies, and programmed cell death in SK-N-AS cells.…”

“…Additionally, in forebrain pyramidal neurons, FOXP1 controlled the expression of genes necessary for spatial cognition and synaptic flexibility 64 . Epilepsy and autism spectrum diseases may result from a genetic variation‐related de novo FOXP1 mutation 65 . The circ ANKMY2/miR106b‐5p axis was found to be able to influence FOXP1 expression in this study.…”

Genetic Etiology Shared by Multiple Sclerosis and Ischemic Stroke

“…Li et al (2015) demonstrated that FOXP1 has vital influences on modulating neuronal migration and morphogenesis in cortical regions. FOXP1 mutations reportedly contribute to nervous system disorders including Huntington disease (Tang et al, 2012), autism (O'Roak et al, 2011;Chien et al, 2013), and epilepsy (Jay et al, 2019). In this study, FOXP1 exhibited an elevated tendency of expression in both MS and IS patients compared to controls (GSE21942: logFC = 1.21; GSE43591: logFC = 0.528; GSE16561: logFC = 0.15, and GSE58294: logFC = 0.34).…”

“… Li et al (2015) demonstrated that FOXP1 has vital influences on modulating neuronal migration and morphogenesis in cortical regions. FOXP1 mutations reportedly contribute to nervous system disorders including Huntington disease ( Tang et al, 2012 ), autism ( O’Roak et al, 2011 ; Chien et al, 2013 ), and epilepsy ( Jay et al, 2019 ).…”