{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:22:14Z","timestamp":1777382534417,"version":"3.51.4"},"reference-count":60,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"abstract":"<jats:p>Introduction: Neurodevelopmental disorders (NDDs) are chronic conditions marked by abnormal brain development, presenting with significant clinical heterogeneity. Early diagnosis is crucial but challenging due to the complex symptoms. Genetic factors play a dominant role in NDD etiology. This study was to evaluate the diagnostic utility of dual-dimension whole-exome sequencing (WES) analysis in Chinese patients with NDDs and to deepen the understanding of genotype-phenotype correlations. Methods: This study retrospectively analyzed WES data of 128 Chinese NDD patients from Hubei Maternal and Child Health Hospital (July 2020\u2013March 2024) for single-nucleotide variants (SNVs)\/small insertions-deletions (Indels) and copy number variants (CNVs). Pathway enrichment, tissue-expression analyses, and functional experiments were conducted to interpret pathogenic genes and variants of uncertain significance. Results: The overall diagnostic rate for NDDs was 35.9% (46\/128), with 28 cases confirmed by SNV\/Indel analysis (30 variants in 29 genes) and 18 by CNV analysis (22 variants). Dual-dimension analysis markedly improved the diagnostic rate compared to conventional SNV\/Indel analysis (35.9% vs. 21.9%). Patients with multisystem abnormalities had a higher diagnostic rate (63.2% vs. 31.2%). Among the 30 SNV\/Indel variants, 86.7% (26) were de novo, and 70.0% (21) were novel. Recurrent pathogenic variants in ASXL3, SHANK3, and EHMT1 genes were identified. Most pathogenic genes were enriched in transcription-regulation pathways and highly expressed in the cerebellum and cerebral cortex. Functional experiments showed that the NLGN3 c.562G&gt;A (p.G188R) hemizygous variant affects protein stability and is deleterious, aiding prenatal diagnosis and the birth of a healthy offspring. Conclusion: Integrating CNV analysis into routine WES workflows effectively clarifies the genetic heterogeneity of NDDs, expands the gene variant spectrum, and provides a basis for NDD prognosis assessment and precision diagnosis and treatment.<\/jats:p>","DOI":"10.1159\/000549155","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T16:01:28Z","timestamp":1761321688000},"page":"1-17","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Characterization of 128 Chinese Individuals with Neurodevelopmental Disorders via Whole-Exome 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