Journal article
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders
Science translational medicine, Vol.6(265), pp.265ra168-265ra168
12/03/2014
DOI: 10.1126/scitranslmed.3010076
PMCID: PMC4286868
PMID: 25473036
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.
Details
- Title: Subtitle
- Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders
- Creators
- Sarah E Soden - University of Missouri–Kansas CityCarol J Saunders - University of Missouri–Kansas CityLaurel K Willig - Children's Mercy HospitalEmily G Farrow - Children's Mercy HospitalLaurie D Smith - Children's Mercy HospitalJosh E Petrikin - Children's Mercy HospitalJean-Baptiste LePichon - Children's Mercy HospitalNeil A Miller - Children's Mercy HospitalIsabelle Thiffault - University of Missouri–Kansas CityDarrell L Dinwiddie - University of New MexicoGreyson Twist - Children's Mercy HospitalAaron Noll - Children's Mercy HospitalBryce A Heese - University of Missouri–Kansas CityLee Zellmer - Children's Mercy HospitalAndrea M Atherton - Children's Mercy HospitalAhmed T Abdelmoity - University of Missouri–Kansas CityNicole Safina - University of Missouri–Kansas CitySarah S Nyp - Children's Mercy HospitalBritton Zuccarelli - Children's Mercy HospitalIngrid A Larson - Children's Mercy HospitalAnn Modrcin - University of Missouri–Kansas CitySuzanne Herd - Children's Mercy HospitalMitchell Creed - Children's Mercy HospitalZhaohui Ye - Johns Hopkins UniversityXuan Yuan - Johns Hopkins UniversityRobert A Brodsky - Johns Hopkins UniversityStephen F Kingsmore - Children's Mercy Hospital
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.6(265), pp.265ra168-265ra168
- DOI
- 10.1126/scitranslmed.3010076
- PMID
- 25473036
- PMCID
- PMC4286868
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Grant note
- U19 HD077693 / NICHD NIH HHS UL1 TR000001 / NCATS NIH HHS TL1 TR000120 / NCATS NIH HHS P20 GM130422 / NIGMS NIH HHS U19HD077693 / NICHD NIH HHS TL1TR000120 / NCATS NIH HHS KL2 TR001448 / NCATS NIH HHS
- Language
- English
- Date published
- 12/03/2014
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984354045802771
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