Effectiveness of exome and genome sequencing guided by acuity of il... - PubMed - NCBI
Genomics|Update|Current
Whole Genome/Exome Sequencing in Practice: Recent Insights
Sci Transl Med. 2014 Dec 3;6(265):265ra168. doi: 10.1126/scitranslmed.3010076.
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.
Soden SE1,
Saunders CJ2,
Willig LK3,
Farrow EG2,
Smith LD3,
Petrikin JE3,
LePichon JB3,
Miller NA4,
Thiffault I5,
Dinwiddie DL6,
Twist G7,
Noll A7,
Heese BA8,
Zellmer L9,
Atherton AM3,
Abdelmoity AT8,
Safina N8,
Nyp SS10,
Zuccarelli B10,
Larson IA4,
Modrcin A8,
Herd S4,
Creed M7,
Ye Z11,
Yuan X11,
Brodsky RA11,
Kingsmore SF2.
Abstract
Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients. Copyright © 2014, American Association for the Advancement of Science.
- PMID:
- 25473036
- [PubMed - in process]
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