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 neurodevel-opmental 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
Varesio C.;Ballante E.;Cabini R. F.;Pasca L.;Orcesi S.;Borgatti R.;Valente E. M.;De Giorgis V.
2021-01-01
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 neurodevel-opmental 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
