Improving diagnostic yield in rare diseases through phenotypic-driven approaches

NDD. Family-based (trio) exome sequencing has become the standardized method for identifying genetic etiologies that cause neurodevelopmental disorders. De novo variants have been responsible for the majority of pathogenic genetic findings, although the landscape of genetic disorders overall is highly heterogeneous. In a recently published study, the authors assessed variant classification to identify new molecular diagnoses and factors influencing the likelihood of receiving a diagnosis. The study reported a diagnostic yield of over 41%, highlighting 60 new genes associated with developmental disorders. The authors also emphasized the importance of structured and detailed phenotypic information for improving variant interpretation. This blog post provides a brief review of their publication in the context of improving diagnostic yield using a phenotypically driven approach in rare diseases.

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