98 Clinical exome sequencing in the diagnosis of autism spectrum disorder

• Published in: Archives of disease in childhood 2021-10, Vol.106 (Suppl 2), p.A41-A41
• Main Authors: Odak, Ljubica, Meašić, Ana-Marija, Bobinec, Adriana, Kero, Mijana, Sansović, Ivona, Vulin, Katarina, Tomić, Mirko, Barišić, Ingeborg
• Format: Article
• Language: English
• Subjects: Abstracts; Autism; Autism Spectrum Disorders; Chromatin remodeling; Deoxyribonucleic acid; Diagnosis; DNA; DNA helicase; DNA-binding protein; DNA-directed RNA polymerase; Environmental factors; Environmental Influences; Environmental risk; Enzymatic activity; Epigenetics; Etiology; Factor analysis; Fragile X syndrome; Gene regulation; Genes; Genetics; Intellectual disabilities; Medical diagnosis; miRNA; Neurodevelopmental disorders; Next-generation sequencing; Patients; Pediatrics; Post-transcription; Regenerative medicine; Regional development; Regional planning; Reproductive health; Risk factors; RNA polymerase; Transcription factors
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2021-europaediatrics.98

The autism spectrum disorder (ASD) is a complex neurodevelopmental disorder whose etiology is still poorly understood and attributed to genetic and environmental factors. The next-generation sequencing (NGS) enables simultaneous detection of pathogenic variants in hundreds of genes involved in the pathogenesis of various diseases. The goal of this study was to determine the role of clinical exome testing in the diagnostics of ASD.For purpose of this study, we analyzed 32 ASD patients that were diagnosed and treated at the Department of Medical Genetics and Reproductive Health in Children’s Hospital Zagreb. After detailed psychiatric evaluation and diagnosis of ASD, all patients underwent a clinical geneticist’s evaluation and clinical exome testing. Chromosomal disorders and fragile X syndrome have been previously excluded in all patients. Clinical exome sequencing has been performed using Illumina TruSight One Kit.Clinical exome analysis revealed pathogenic variants in 8 out of 32 analysed patients (25%). Pathogenic variants were found in genes: CAMTA1 (transcription factor), DEAF1 (transcription factor expressed in the brain), BCORL1 (transcriptional corepressor), EP300 (chromatin remodeling transcription factor), DICER1 (posttranscriptional microRNAs modulator), MED13 (regulation of DNA-binding transcription and RNA polymerase II factor activation), CHD7 (chromo domain helicase DNA-binding protein 7) and in SGSH gene (N-sulfoglucosamine sulfohydrolase). Benign variants and variants of unknown signifficane were present in 9 out of 32 patients (28.1%). Secondary findings, unrelated to primary indication were noted in 5 out of 32 patients (15.6%).The remaining patients had normal clinical exome testing results (31.3%).Clinical exome sequencing disclosed genetic background in 25% of ASD patients, identifying pathogenic gene variants that are involved in fundamental cell processes, protein expression and enzyme activity in the brain. Despite the high diagnostic yield, the etiology of ASD remains still unknown in the majority of patients. Additional investigations, including whole-exome sequencing, epigenetic testing and environmental risk factor analysis are necessary to better define a complex genetic architecture and environmental risks in ASD.AcknowledgmentThis work was supported by Scientific Center of Excellence for Reproductive and Regenerative Medicine and by the EU through the European Regional Development Fund, under grant agreement No.KK.01.1.1.01.