Background: The advent of next-generation sequencing (NGS) techniques in clinical practice led to a significant advance in gene discovery. We aimed to describe diagnostic yields of a “dynamic” exome-based approach in a cohort of patients with epilepsy associated with neurodevelopmental disorders. Methods: We conducted a retrospective, observational study on 72 probands. All patients underwent a first diagnostic level of a 135 gene panel, a second of 297 genes for inconclusive cases, and finally, a whole-exome sequencing for negative cases. Diagnostic yields at each step and cost-effectiveness were the objects of statistical analysis. Results: Overall diagnostic yield in our cohort was 37.5%: 29% of diagnoses derived from the first step analysis, 5.5% from the second step, and 3% from the third. A significant difference emerged between the three diagnostic steps (p < 0.01), between the first and second (p = 0.001), and the first and third (p << 0.001). The cost-effectiveness plane indicated that our exome-based “dynamic” approach was better in terms of cost savings and higher diagnostic rate. Conclusions: Our findings suggested that “dynamic” NGS techniques applied to well-phenotyped individuals can save both time and resources. In patients with unexplained epilepsy comorbid with NDDs, our approach might maximize the number of diagnoses achieved.

Diagnostic Yield and Cost-Effectiveness of "Dynamic" Exome Analysis in Epilepsy with Neurodevelopmental Disorders: A Tertiary-Center Experience in Northern Italy / C. Varesio, S. Gana, A. Asaro, E. Ballante, R.F. Cabini, E. Tartara, M. Bagnaschi, L. Pasca, M. Valente, S. Orcesi, C. Cereda, P. Veggiotti, R. Borgatti, E.M. Valente, V. De Giorgis. - In: DIAGNOSTICS. - ISSN 2075-4418. - 11:6(2021 Jun), pp. 948.1-948.10. [10.3390/diagnostics11060948]

Diagnostic Yield and Cost-Effectiveness of "Dynamic" Exome Analysis in Epilepsy with Neurodevelopmental Disorders: A Tertiary-Center Experience in Northern Italy

P. Veggiotti;V. De Giorgis
Ultimo
2021-06

Abstract

Background: The advent of next-generation sequencing (NGS) techniques in clinical practice led to a significant advance in gene discovery. We aimed to describe diagnostic yields of a “dynamic” exome-based approach in a cohort of patients with epilepsy associated with neurodevelopmental disorders. Methods: We conducted a retrospective, observational study on 72 probands. All patients underwent a first diagnostic level of a 135 gene panel, a second of 297 genes for inconclusive cases, and finally, a whole-exome sequencing for negative cases. Diagnostic yields at each step and cost-effectiveness were the objects of statistical analysis. Results: Overall diagnostic yield in our cohort was 37.5%: 29% of diagnoses derived from the first step analysis, 5.5% from the second step, and 3% from the third. A significant difference emerged between the three diagnostic steps (p < 0.01), between the first and second (p = 0.001), and the first and third (p << 0.001). The cost-effectiveness plane indicated that our exome-based “dynamic” approach was better in terms of cost savings and higher diagnostic rate. Conclusions: Our findings suggested that “dynamic” NGS techniques applied to well-phenotyped individuals can save both time and resources. In patients with unexplained epilepsy comorbid with NDDs, our approach might maximize the number of diagnoses achieved.
epilepsy; neurodevelopmental disorders; developmental epileptic encephalopathies; next-generation sequencing techniques; exome sequencing; virtual genetic panels; dynamic approach
Settore MED/39 - Neuropsichiatria Infantile
25-mag-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/848635
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