Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.

Juan Xiong,Jing Peng,Fei Yin,Nan Pang,Xiaolu Deng,Lifen Yang,Liwen Wu,Fang He,Shimeng Chen,Chen Chen

doi:10.3389/fnins.2019.00349

Abstract

Autism spectrum disorder (ASD) is frequently comorbid with other neurological disorders such as intellectual disability (ID) or global development delay (GDD) and epilepsy. The pathogenesis of ASD is complex. So far, studies have identified more than 1000 ASD risk genes. Most of them were also reported to relate with other neurological diseases, and only several of them have been confirmed as pathogenic genes for autism. Little is known about the roles of these risk genes in neurological diseases with ASD. In the present study, we recruited a cohort of 158 neurological disorder probands with 163 variants of 48 ASD risk genes. Of these, 50 individuals (31.6%) were diagnosed with ASD. In the ASD patient subset, we identified several rarely reported candidate genes including DOLK, USH2A, and HUWE1. In a comparison of patients with neurological disorders with and without ASD, we found that ID/GDD was frequently comorbid with ASD whereas epilepsy was more common in the non-ASD group. Statistical analyses of all possible risk factors implicated that variants in synaptic genes, especially non-voltage-gated ion channel genes and in transcriptional and chromosome genes were related to ASD, but none of the investigated environmental factors was. Our results are useful for the future diagnosis and prognosis of patients with neurological disorders and emphasize the utility of genetic screening.

Highlights

Autism spectrum disorder (ASD), a common neurodevelopmental disorder, is characterized by deficiency in social communication and interaction and restricted, repetitive behaviors (Lai et al, 2014)
ASD risk genes were identified according to the SFARI Gene database2
Our data combined next-generation sequencing results with segregation analysis demonstrates that 163 variants in 48 ASD risk genes underlie at or associated to a subset of neurological disease in children, but autistic traits are not observed in every individual

Summary

Introduction

Autism spectrum disorder (ASD), a common neurodevelopmental disorder, is characterized by deficiency in social communication and interaction and restricted, repetitive behaviors (Lai et al, 2014). ASD is often associated with other neurological comorbidities such as epilepsy and intellectual disability (ID) (Yeargin-Allsopp et al, 2003; Sundelin et al, 2016). This phenomenon indicates a possible shared etiology between ASD and other neurological diseases. Recent studies have shown that neurological disorders such as epilepsy and ID are multifactorial and involve both genetic and environmental contributions (Chiurazzi and Pirozzi, 2016; Mazarati et al, 2017; Bozzi et al, 2018). The increasing prevalence of genetic testing has permitted the discovery of various relationships between multiple genes and various neurological disorders. ASD has 1007 risk genes as per the SFARI Gene database, an evolving database of genes that are implicated in

Methods

Results

Conclusion