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https://hdl.handle.net/2440/140538
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Type: | Journal article |
Title: | Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort |
Author: | Dias, K.-R. Shrestha, R. Schofield, D. Evans, C.-A. O'Heir, E. Zhu, Y. Zhang, F. Standen, K. Weisburd, B. Stenton, S.L. Sanchis-Juan, A. Brand, H. Talkowski, M.E. Ma, A. Ghedia, S. Wilson, M. Sandaradura, S.A. Smith, J. Kamien, B. Turner, A. et al. |
Citation: | Genetics in Medicine, 2024; 26(5):101076-101076 |
Publisher: | Elsevier |
Issue Date: | 2024 |
ISSN: | 1098-3600 1098-3600 |
Statement of Responsibility: | Kerith-Rae Dias ... Futao Zhang ... Susan M. White ... Matthew F. Hunter, Lauren Akesson ... Mark A. Corbett, Thessa Kroes, Jozef Gecz ... et al. |
Abstract: | Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively. Methods: The ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID. Results: The ES diagnostic yield was 42/74 (57%). GS diagnoses were made in 9/32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8/9 SNVs/CNVs undetected in older ES, confirming a GS-unique diagnostic rate of 1/32 (3%). Episignatures contributed diagnostic information in 9% with GS-corroboration in 1/32 (3%) and diagnostic clues in 2/32 (6%). A genetic aetiology for ID was detected in 51/74 (69%) families. 12 candidate disease genes were identified. Contemporary ES followed by GS cost US$4,976 (95% CI: $3,704; $6,969) per diagnosis and first-line GS at a cost of $7,062 (95% CI: $6,210; $8,475) per diagnosis. Conclusion: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2,435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost. |
Keywords: | episignature exome-negative genome sequencing health economics intellectual disability |
Description: | Published online: January 19, 2024 |
Rights: | © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.gim.2024.101076 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.1016/j.gim.2024.101076 |
Appears in Collections: | Research Outputs |
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