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

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Molecular Diagnostics

Background:

• Autism spectrum disorder (ASD) is a neurodevelopmental condition with significant genetic underpinnings.
• Genetic testing is crucial for understanding ASD etiology and developing diagnostic tools.
• Previous genetic analyses often yield negative results in individuals with ASD.

Purpose of the Study:

• To implement and evaluate a personalized next-generation sequencing (NGS) panel, AutismSeq, for diagnosing essential autism spectrum disorder (ASD).
• To assess the diagnostic efficacy and cost-effectiveness of AutismSeq in a clinical setting.
• To investigate the genetic heterogeneity of ASD in patients with negative results from standard genetic tests.

Main Methods:

• Prospective implementation of a customized NGS panel (AutismSeq) over four years.
• Analysis of a cohort of 48 individuals (age >3 years) meeting DSM-5 criteria for ASD.
• Comparison of NGS results with prior genetic testing, including chromosomal microarray, karyotype, fragile-X, and MLPA/FISH.

Main Results:

• AutismSeq detected pathogenic or likely pathogenic variants in 11 individuals and variants of uncertain significance (VUS) in 10 individuals.
• These findings were in patients previously negative for chromosomal microarray and other genetic analyses.
• The study highlighted the genetic heterogeneity and diagnostic challenges in ASD.

Conclusions:

• A personalized NGS panel like AutismSeq demonstrates good diagnostic efficacy for essential ASD in routine clinical care.
• NGS-based panels are valuable for identifying genetic variants missed by conventional genetic testing in ASD patients.
• The AutismSeq panel is potentially cost-effective for genetic laboratories and aids in the molecular diagnosis of ASD.