Publication
Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield
Gubbels C, VanNoy G, Madden J, Copenheaver D, Yang S, Wojcik M, Gold N, Genetti C, Stoler J, Parad R, Roumiantsev S, Bodamer O, Beggs A, Juusola J, Agrawal P, Yu T · Genet Med · 2020
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.
Synced from the TRENDS in Pediatric Palliative Care Zotero library, curated by The Siden Research Team. ICPCN does not host or verify the full text.