Dataset Information

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.

ABSTRACT:

Background

Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array-comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD.

Methods

The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent.

Results

Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array-CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests.

Conclusions

This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in-depth care of children with autism when genetic results are analyzed also with a focus on patient management.

SUBMITTER: Cucinotta F

PROVIDER: S-EPMC10422062 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.

Cucinotta Francesca F Lintas Carla C Tomaiuolo Pasquale P Baccarin Marco M Picinelli Chiara C Castronovo Paola P Sacco Roberto R Piras Ignazio Stefano IS Turriziani Laura L Ricciardello Arianna A Scattoni Maria Luisa ML Persico Antonio M AM

Molecular genetics & genomic medicine 20230425 8

<h4>Background</h4>Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array-comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD.<h4>Methods</h4>The aim of this study was to evaluate both diagnostic yield a ...[more]

PMID: 37186221

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Project description:ObjectiveClinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic review of the success rate (diagnostic yield) of clinical sequencing through next-generation sequencing (NGS) across NDDs. We compare the genetic testing yield across NDD subtypes and sequencing technology.MethodsWe performed a systematic review of the PubMed literature until May 2020. We included clinical sequencing studies that utilized NGS in individuals with epilepsy, autism spectrum disorder (ASD), or intellectual disability (ID). Data were extracted, reviewed, and categorized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators performed clinical evaluation and grouping following the International League Against Epilepsy (ILAE) guidelines. Pooled rates of the diagnostic yield and 95% confidence intervals were estimated with a random-effects model.ResultsWe identified 103 studies (epilepsy, N = 72; ASD, N = 14; ID, N = 21) across 32,331 individuals. Targeted gene panel sequencing was used in 73, and exome sequencing in 36 cohorts. Given highly selected patient cohorts, the diagnostic yield was 17.1% for ASD, 24% for epilepsy, and 28.2% for ID (23.7% overall). The highest diagnostic yield for epilepsy subtypes was observed in individuals with ID (27.9%) and early onset seizures (36.8%). The diagnostic yield for exome sequencing was higher than for panel sequencing, even though not statistically significant (27.2% vs 22.6%, P = .071). We observed that clinical sequencing studies are performed predominantly in countries with a high Inequality-adjusted Human Development Index (IHDI) (countries with sequencing studies: IHDI median = 0.84, interquartile range [IQR] = 0.09 vs countries without sequencing studies: IHDI median = 0.56, IQR = 0.3). No studies from Africa, India, or Latin America were identified, indicating potential barriers to genetic testing.SignificanceThis meta-analysis and systematic review provides a comprehensive overview of clinical sequencing studies of NDDs and will help guide policymaking and steer decision-making in patient management.

Dataset Information

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.

Background

Methods

Results

Conclusions

Publications

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.

Similar Datasets

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