Abstract
Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal congenital lung disorder associated with heterozygous variants in the FOXF1 gene or its regulatory region. Patients with ACD/MPV unnecessarily undergo invasive and expensive treatments while awaiting a diagnosis. The aim of this study was to reduce the time to diagnose ACD/MPV by developing a targeted next-generation sequencing (NGS) panel that detects FOXF1 variants. Methods: A FOXF1-targeted NGS panel was developed for detection of mutations and large genomic alterations and used for retrospective testing of ACD/MPV patients and controls. Results were confirmed with Sanger sequencing and SNP array analysis. Results: Each amplicon of the FOXF1-targeted NGS panel was efficiently sequenced using DNA isolated from blood or cell lines of 15 ACD/MPV patients and 8 controls. Moreover, testing of ACD/MPV patients revealed six novel and six previously described pathogenic or likely pathogenic FOXF1 alterations. Conclusion: We successfully designed a fast and reliable targeted genetic test to detect variants in the FOXF1 gene and its regulatory region in one run. This relatively noninvasive test potentially prevents unnecessary suffering for patients and reduces the use of futile and expensive treatments like extra-corporeal membrane oxygenation. Impact: FOXF1-targeted NGS potentially prevents ACD/MPV patients from unnecessary suffering and expensive treatments.FOXF1-targeted NGS potentially reduces the number of misdiagnosis in ACD/MPV patients.Retrospective testing of ACD/MPV patients using FOXF1-targeted NGS revealed six novel pathogenic or likely pathogenic variants.
Original language | English |
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Pages (from-to) | 518-525 |
Number of pages | 8 |
Journal | Pediatric Research |
Volume | 89 |
Issue number | 3 |
Early online date | 15 May 2020 |
DOIs | |
Publication status | Published - Feb 2021 |
Bibliographical note
Funding Information:We thank the VU University Medical Center Amsterdam and the Charles University and General University Hospital Prague for their contribution to our sample collection. Further, we thank the Friends from Sophia Foundation for their support and, we thank the Royal Netherlands Academy of Arts and Sciences for the Ter Meulen Grant. We received financial support from The Friends from Sophia Foundation and The Royal Netherlands Academy of Arts and Sciences.
Publisher Copyright:
© 2020, International Pediatric Research Foundation, Inc.