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Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield.
- Source :
-
Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2020 Apr; Vol. 22 (4), pp. 736-744. Date of Electronic Publication: 2019 Nov 29. - Publication Year :
- 2020
-
Abstract
- Purpose: To investigate the impact of rapid-turnaround exome sequencing in critically ill neonates using phenotype-based subject selection criteria.<br />Methods: Intensive care unit babies aged <6 months with hypotonia, seizures, a complex metabolic phenotype, and/or multiple congenital malformations were prospectively enrolled for rapid (<7 day) trio-based exome sequencing. Genomic variants relevant to the presenting phenotype were returned to the medical team.<br />Results: A genetic diagnosis was attained in 29 of 50 (58%) sequenced cases. Twenty-seven (54%) patients received a molecular diagnosis involving known disease genes; two additional cases (4%) were solved with pathogenic variants found in novel disease genes. In 24 of the solved cases, diagnosis had impact on patient management and/or family members. Management changes included shift to palliative care, medication changes, involvement of additional specialties, and the consideration of new experimental therapies.<br />Conclusion: Phenotype-based patient selection is effective at identifying critically ill neonates with a high likelihood of receiving a molecular diagnosis via rapid-turnaround exome sequencing, leading to faster and more accurate diagnoses, reducing unnecessary testing and procedures, and informing medical care.
Details
- Language :
- English
- ISSN :
- 1530-0366
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Genetics in medicine : official journal of the American College of Medical Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 31780822
- Full Text :
- https://doi.org/10.1038/s41436-019-0708-6