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Identification of novel single-nucleotide variants altering RNA splicing of PKD1 and PKD2

Journal of Human Genetics volume 67, pages 27–34 (2022)Cite this article

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Abstract

The development of sequencing techniques identified numerous genetic variants, and accurate evaluation of the clinical significance of these variants facilitates the diagnosis of Mendelian diseases. In the present study, 549 rare single- nucleotide variants of uncertain significance were extracted from the ADPKD and ClinVar databases. MaxEntScan scoresplice is an in silico splicing prediction tool that was used to analyze rare PKD1 and PKD2 variants of unknown significance. An in vitro minigene splicing assay was used to verify 37 splicing-altering candidates that were located within seven residues of the splice donor sequence excluding canonical GT dinucleotides or within 21 residues of the acceptor sequence excluding canonical AG dinucleotides of PKD1 and PKD2. We demonstrated that eight PKD1 variants alter RNA splicing and were predicted to be pathogenic.

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Data availability

The data used to support this study are available from the corresponding author upon request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no 81871203).

Funding

Y.Y. is funded by the National Natural Science Foundation of China, grant/award number: 81871203.

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Authors and Affiliations

  1. Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China

    Shengyu Xie, Xiangyou Leng, Dachang Tao, Yangwei Zhang, Zhaokun Wang, Xinyue Zhang, Tianrong He, Xiaolan Tan, Yunqiang Liu & Yuan Yang

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  1. Shengyu Xie
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Contributions

S.X. participation in the whole study, drafting of the manuscript, and data analysis; S.X., X.L., Y.Z., Z.W., X.Z., T.H., and X.T. carried out the experiments; D.T. and Y.L. data curation; Y.Y. writing—review, editing, correspondence, and proofs of the manuscript.

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Correspondence to Yuan Yang.

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Xie, S., Leng, X., Tao, D. et al. Identification of novel single-nucleotide variants altering RNA splicing of PKD1 and PKD2. J Hum Genet 67, 27–34 (2022). https://doi.org/10.1038/s10038-021-00959-1

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