Koay, Bee Tee and Chiow, Mei Yee and Ismail, Jamiila and Fahmy, Norfarhana Khairul and Yee, Seow Yeing and Mustafa, Norhazlin and Arip, Masita and Ripen, Adiratna Mat and Mohamad, Saharuddin (2022) Visual inspection reveals a novel pathogenic mutation in PKD1 missed by the variant caller in whole-exome sequencing. Molecular Medicine Reports, 26 (6). ISSN 1791-2997, DOI https://doi.org/10.3892/mmr.2022.12882.
Full text not available from this repository.Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common type of inherited cystic kidney disease. The feasibility of whole-exome sequencing (WES) to obtain molecular diagnosis of ADPKD is still in question as previous studies showed conflicting results. Utilizing WES on a patient with ADPKD, standard bioinformatics pipeline demonstrated no pathogenic variant in the genes of interest. By visualizing read alignments using the Integrative Genomics Viewer, a region with atypical alignment of numerous soft-clipped reads at exon 45 of polycystin 1, transient receptor potential channel interacting (PKD1) gene was demonstrated. A total of four visual inspection steps were outlined to assess the origin of these soft-clipped reads as strand bias during capture, poor mapping, sequencing error or DNA template contamination. Following assessment, the atypical alignment at PKD1 was hypothesized to be caused by an insertion/deletion mutation. Sanger sequencing confirmed the presence of a novel 20-bp insertion in PKD1 (NM_001009944.3; c.12143_12144insTCCCCGCAGTCTTCCCCGCA; p.Val4048LeufsTer157), which introduced a premature stop codon and was predicted to be pathogenic. The present study demonstrated that WES could be utilized as a molecular diagnostic tool for ADPKD. Furthermore, visual inspection of read alignments was key in identifying the pathogenic variant. The proposed visual inspection steps may be incorporated into a typical WES data analysis workflow to improve the diagnostic yield.
| Item Type: | Article |
|---|---|
| Funders: | None |
| Uncontrolled Keywords: | WES; ADPKD; IGV; Visual inspection; Soft-clipped; Polycystin 1; Transient receptor potential channel interacting |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 14 Nov 2023 07:37 |
| Last Modified: | 14 Nov 2023 07:37 |
| URI: | http://eprints.um.edu.my/id/eprint/40709 |
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