Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield

Title

Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield

Creator

Gubbels CS; VanNoy GE; Madden JA; Copenheaver D; Yang S; Wojcik MH; Gold NB; Genetti CA; Stoler J; Parad RB; Roumiantsev S; Bodamer O; Beggs AH; Juusola J; Agrawal PB; Yu TW

Publisher

Genetics in Medicine

Date

2020

Subject

Aged; Critical Illness; exome sequencing; Exome/genetics; Genetic Testing; Humans; Infant; Infant Newborn; intensive care unit; neonates; Phenotype; Prospective Studies; Whole Exome Sequencing

Description

PURPOSE: To investigate the impact of rapid-turnaround exome sequencing in critically ill neonates using phenotype-based subject selection criteria. 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. 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. 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.

Rights

Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).

Citation List Month

June 2021 List

Collection

Citation

Gubbels CS; VanNoy GE; Madden JA; Copenheaver D; Yang S; Wojcik MH; Gold NB; Genetti CA; Stoler J; Parad RB; Roumiantsev S; Bodamer O; Beggs AH; Juusola J; Agrawal PB; Yu TW, “Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield,” Pediatric Palliative Care Library, accessed August 3, 2021, https://pedpalascnetlibrary.omeka.net/items/show/17568.

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