{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:57:36Z","timestamp":1773035856530,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by pathogenic variants of <jats:italic>PKD1<\/jats:italic> and <jats:italic>PKD2<\/jats:italic>. Compared to <jats:italic>PKD2<\/jats:italic>\u2010related patients, patients with <jats:italic>PKD1<\/jats:italic> pathogenic variants have more severe symptoms, present a gradual decline in renal function, and finally progress to end\u2010stage kidney disease with an earlier mean onset age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, trio exome sequencing (ES) was performed to reveal the genetic etiology in a Chinese family clinically diagnosed with polycystic kidney, followed by validation through Sanger sequencing on both genomic DNA and cDNA levels. Subsequently, targeted preimplantation genetic testing was provided for the family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous <jats:italic>PKD1<\/jats:italic> variant (c.1717_1722+11del) was detected in the proband and other clinically\u2010affected relatives. Interestingly, cDNA sequencing demonstrated that the variant, despite being annotated as non\u2010frameshift within exon 8, impacted the splicing of <jats:italic>PKD1<\/jats:italic>. Two abnormal transcription products were formed: one induced frameshift, while the other caused 133 amino acids to be inserted between exon 8 and exon 9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study revealed a novel <jats:italic>PKD1<\/jats:italic> variant using ES as the cause of ADPKD in a Chinese family with multiple affected members. The variant at the exon\u2010intron boundary would induce alternative splicing, which should not be excluded from genetic analysis. Validated on the cDNA level could provide more comprehensive genetic information for disease stratification. And the novel variant expands the spectrum of <jats:italic>PKD1<\/jats:italic> variants in ADPKD. The recurrent risk could be blocked accordingly for the families' offspring.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2217","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T01:56:31Z","timestamp":1686102991000},"source":"Crossref","is-referenced-by-count":4,"title":["A novel heterozygous <scp><i>PKD1<\/i><\/scp> variant causing alternative splicing in a Chinese family with autosomal dominant polycystic kidney disease"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-4827","authenticated-orcid":false,"given":"Qianying","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medical Genetics West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Department of Obstetrics and Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), 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