Academic Journal
Contribution of Copy Number Variants and Cumulative Genetic Load to Autism Spectrum Disorders: Integrative Insights from Chromosomal Microarray Analysis.
| Τίτλος: | Contribution of Copy Number Variants and Cumulative Genetic Load to Autism Spectrum Disorders: Integrative Insights from Chromosomal Microarray Analysis. |
|---|---|
| Συγγραφείς: | Di Iorio MR; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy., La Monica I; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy.; Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy., Imperatore A; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy., Sica A; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy.; Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy., Iorio V; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy.; Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy., Pastore L; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy.; Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy., Lombardo B; CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 486, 80145 Naples, Italy.; Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy. |
| Πηγή: | International journal of molecular sciences [Int J Mol Sci] 2026 Aug 20; Vol. 27 (16). Date of Electronic Publication: 2026 Aug 20. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| Ιατρικοί όροι (MeSH): | DNA Copy Number Variations*/genetics , Autism Spectrum Disorder*/genetics, Humans ; Comparative Genomic Hybridization ; Female ; Male ; Child ; Phenotype ; Child, Preschool ; Genetic Predisposition to Disease ; Retrospective Studies ; Adolescent |
| Περίληψη: | Autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDDs) are characterized by a complex genetic architecture involving both rare high-impact variants and cumulative low-effect alterations. The contribution of borderline copy number variants (CNVs) to disease susceptibility and phenotypic variability remains incompletely understood. Reflecting a real-world clinical setting rather than a prospectively recruited research cohort, we performed a retrospective analysis of a tertiary care registry comprising 328 individuals referred for suspected ASD or NDDs who underwent array comparative genomic hybridization (a-CGH), identifying 612 CNVs classified according to ACMG/ClinGen guidelines. CNVs were evaluated by type, size, genomic distribution, and clinical correlation, and patients were stratified based on CNV burden and the presence of borderline variants. Duplications were more frequent than deletions, and medium-sized CNVs (100-500 kb) were the most common. Borderline CNVs represented the largest category. Within this descriptive cohort, increased CNV burden, in both number and cumulative genomic size, co-occurred more frequently in individuals with severe phenotypes, including ASD with intellectual disability, epilepsy, and broader NDDs. Individuals with isolated ASD showed a lower burden and enrichment of small borderline variants, which often co-occurred alongside CNVs. In contrast, severe phenotypes were frequently associated with single large pathogenic variants. Recurrent loci included 15q11.2-q13, 16p11.2, and 22q11.21. Overall, these exploratory observations from a real-world clinical registry illustrate how cumulative genomic burden and borderline CNVs co-occur across different neurodevelopmental presentations, providing descriptive context for future mechanistic studies. |
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| Contributed Indexing: | Keywords: CNV burden; array comparative genomic hybridization; autism spectrum disorders; copy number variants |
| Entry Date(s): | Date Created: 20260827 Date Completed: 20260827 Latest Revision: 20260829 |
| Update Code: | 20260829 |
| PubMed Central ID: | PMC13513768 |
| DOI: | 10.3390/ijms27167434 |
| PMID: | 42653435 |
| Βάση Δεδομένων: | MEDLINE |
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