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Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.
- Source :
-
Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 May; Vol. 26 (5), pp. 101076. Date of Electronic Publication: 2024 Jan 19. - Publication Year :
- 2024
-
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.<br />Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID.<br />Results: The ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis.<br />Conclusion: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2435, 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.<br />Competing Interests: Conflict of Interest The authors declare no conflicts of interest.<br /> (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Male
Female
Cohort Studies
Genetic Testing economics
Genetic Testing methods
Whole Genome Sequencing economics
Child
Genome, Human genetics
DNA Copy Number Variations genetics
Polymorphism, Single Nucleotide genetics
Child, Preschool
Intellectual Disability genetics
Intellectual Disability diagnosis
Exome genetics
Exome Sequencing economics
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0366
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Genetics in medicine : official journal of the American College of Medical Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 38258669
- Full Text :
- https://doi.org/10.1016/j.gim.2024.101076