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REFINEMENT OF NEWBORN SCREENING FOR CYSTIC FIBROSIS WITH NEXT GENERATION SEQUENCING
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  • Michael Rock,
  • Mei W. Baker,
  • Nicholas Antos,
  • Philip Farrell
Michael Rock
University of Wisconsin-Madison Department of Pediatrics

Corresponding Author:[email protected]

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Mei W. Baker
University of Wisconsin-Madison Department of Pediatrics
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Nicholas Antos
Medical College of Wisconsin Department of Pediatrics
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Philip Farrell
University of Wisconsin-Madison Department of Pediatrics
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Abstract

Background: Newborn screening (NBS) for cystic fibrosis (CF) has been underway universally in the USA for more than a decade, as well in most European countries, and algorithms have been evolving throughout this period with quality improvement projects as immunoreactive trypsinogen determinations alone have been transformed to a 2-tier strategy with DNA analyses. Objective: To apply next generation sequencing (NGS) as a method for expanding the DNA tier for identifying variants in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene with minimization of unintended outcomes. Design: Sequential quality improvement project in three phases using plan coupled to statewide follow up and analysis of screening outcomes in comparison to other NBS programs that use CFTR sequencing. Results: After demonstrating feasibility in the first phase, we studied an IRT/NGS algorithm that included CFTR Variants with Varying Clinical Consequences (VVCCs). This revealed a high identification of CF patients with 2-variants detected through screening, but for every CF case there were 1.4 with cystic fibrosis metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID). This led us to a third phase of quality improvement in which the VVCCs were eliminated except for R117H, resulting in 94% 2-variant detection of patients and 0.44:1 ratio of CRMS/CFSPID to CF. Conclusion: NGS can be used with IRT as an effective method of identifying infants at risk for CF without an appreciable increase in detection of either carriers or CRMS/CFSPID cases.
31 Mar 2022Submitted to Pediatric Pulmonology
09 Apr 2022Submission Checks Completed
09 Apr 2022Assigned to Editor
13 Apr 2022Reviewer(s) Assigned
15 May 2022Review(s) Completed, Editorial Evaluation Pending
29 May 2022Editorial Decision: Revise Major
01 Aug 20221st Revision Received
07 Aug 2022Reviewer(s) Assigned
07 Aug 2022Submission Checks Completed
07 Aug 2022Assigned to Editor
12 Sep 2022Review(s) Completed, Editorial Evaluation Pending
20 Sep 2022Editorial Decision: Revise Minor
30 Sep 20222nd Revision Received
07 Oct 2022Submission Checks Completed
07 Oct 2022Assigned to Editor
07 Oct 2022Reviewer(s) Assigned
02 Nov 2022Review(s) Completed, Editorial Evaluation Pending
07 Nov 2022Editorial Decision: Revise Minor
12 Nov 20223rd Revision Received
15 Nov 2022Assigned to Editor
15 Nov 2022Submission Checks Completed
15 Nov 2022Review(s) Completed, Editorial Evaluation Pending
15 Nov 2022Reviewer(s) Assigned
16 Nov 2022Editorial Decision: Accept