Naslov
Clinical exome sequencing in the diagnosis of autism spectrum disorder

Autori
Odak, Ljubica ; Meašić, Ana-Marija ; Bobinec, Adriana ; Kero, Mijana ; Sansović, Ivona ; Vulin, Katarina ; Tomić, Mirko ; Barišić, Ingeborg.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
WebArchives of Disease in Childhood / - , 2021, A41-A41

Skup
10th Europaediatrics 2021

Mjesto i datum
Zagreb, Hrvatska, 07.10.2021. - 09.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Clinical exome sequencing ; autism spectrum disorder

Sažetak
The autism spectrum disorder (ASD) is a complex neurodevelopmental disorder whose etiology is still poorly understood and attributed to genetic and environmental factors. The nextgeneration 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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