Randomized trial demonstrates enhanced understanding of genetic variants in neurodevelopmental disorders, indicating the importance of expert-driven analysis.
Key Points
The study aims to explore the complexities of diagnosing neurodevelopmental disorders through comprehensive genetic analysis and phenotyping.
Analysed genetic data from 419 Italian neurodevelopmental disorder patient-parent trios.
Utilized exome sequencing to establish molecular diagnoses and assess variant pathogenicity.
Conducted manual curation and deep phenotyping to refine gene-disease correlations.
Exome sequencing provided a molecular diagnosis in 36.5% of cases and 53.8% in syndromic presentations.
Identified pathogenic splicing defects misclassified as missense or stop-gain variants, confirmed through functional analysis.
Refined gene-disease correlations, supporting DSCAM as a high-confidence risk gene and discovering a novel GNAI2-related syndrome.