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. 2023 Nov 17;14(11):2091.
doi: 10.3390/genes14112091.

NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital

Ana Karen Sandoval-Talamantes  1 , Jair Antonio Tenorio-Castaño  1   2   3 , Fernando Santos-Simarro  1   2   3 , Carmen Adán  1 , María Fernández-Elvira  1 , Laura García-Fernández  1 , Yolanda Muñoz  1 , Pablo Lapunzina  1   2   3 , Julián Nevado  1   2   3
Affiliations

NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital

Ana Karen Sandoval-Talamantes et al. Genes (Basel). .

Abstract

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories.

Keywords: NGS; autistic spectrum disorder; panel; tertiary hospital.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient selection algorithm. ASD—Autistic Spectrum Disorder; FISH—fluorescence in situ hybridization; MLPA—Multiplex Ligation-Dependent Probe Amplification; CMA—Chromosomal Microarray Analysis; NGS—Next Generation Sequencing.
Figure 2
Figure 2
Distribution of the NGS panel results. Percentage of cases with “pathogenic” (P/LP or VUS-LP), VUS variants, and those patients without changes found by NGS. P/LP—pathogenic/probably pathogenic; VUS—variants of uncertain significance.
Figure 3
Figure 3
Groups of genes with pathogenic variations were detected using the NGS panel (AutismSeq) in their association with epilepsy, intellectual disability, or genetic syndromes.
Figure 4
Figure 4
Analysis of the diagnostic algorithm for ASD using array-CGH (KaryoArray®)/NGS panel (AutismSeq).
See this image and copyright information in PMC

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