Diagnostic yield of a targeted gene panel in primary ciliary dyskinesia patients.

Autor: Paff T; Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.; Department of Pediatric Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Kooi IE; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Moutaouakil Y; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Riesebos E; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Sistermans EA; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Daniels HJMA; Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands., Weiss JMM; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Niessen HHWM; Department of Pathology and Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands., Haarman EG; Department of Pediatric Pulmonology, VU University Medical Center, Amsterdam, The Netherlands., Pals G; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands., Micha D; Department of Clinical Genetics, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2018 May; Vol. 39 (5), pp. 653-665. Date of Electronic Publication: 2018 Mar 09.
DOI: 10.1002/humu.23403
Abstrakt: We aimed to determine the diagnostic yield of a targeted-exome panel in a cohort of 74 Dutch primary ciliary dyskinesia (PCD) patients. The panel consisted of 26 PCD-related and 284 candidate genes. To prioritize PCD candidate genes, we investigated the transcriptome of human airway cells of 12 healthy volunteers during in vitro ciliogenesis and hypothesized that PCD-related genes show significant upregulation. We compared gene expression in epithelial precursor cells grown as collagen monolayer and ciliated cells grown in suspension by RNA sequencing. All genes reported as PCD causative, except NME8, showed significant upregulation during in vitro ciliogenesis. We observed 67.6% diagnostic yield when testing the targeted-exome panel in our cohort. There was relatively high percentage of DNAI and HYDIN mutations compared to other countries. The latter may be due to our solution for the problem of the confounding HYDIN2 pseudogene. Candidate genes included two recently published PCD-related genes DNAJB13 and PIH1D3; identification of the latter was a direct result of this study. In conclusion, we demonstrate 67.6% diagnostic yield by targeted exome sequencing in a Dutch PCD population and present a highly sensitive and moderately specific approach for identification of PCD-related genes, based on significant upregulation during in vitro ciliogenesis.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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