{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:01:48Z","timestamp":1786114908473,"version":"build-2736575974"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Autosomal dominant polycystic kidney disease (ADPKD) is most commonly caused by pathogenic variants in\n                      <jats:italic>PKD1<\/jats:italic>\n                      . Here, we reported the functional characterization of an intronic\n                      <jats:italic>PKD1<\/jats:italic>\n                      variant identified in an ADPKD-affected family and its subsequent application in preimplantation genetic testing for monogenic disorders (PGT-M).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A three-generation ADPKD family was enrolled. Whole-exome sequencing revealed a heterozygous\n                      <jats:italic>PKD1<\/jats:italic>\n                      c.7489 + 5G&amp;gt;A variant, which co-segregated with the disease and was initially classified as a variant of uncertain significance. A minigene assay demonstrated that the variant induced skipping of exon 18, leading to a frameshift (p.Arg2404Valfs*123), supporting its reclassification as pathogenic. The couple underwent PGT-M using trophectoderm biopsy, haplotype linkage analysis, and direct mutation detection. An unaffected pregnancy was achieved, and subsequent prenatal diagnosis confirmed the absence of the variant and a normal chromosomal karyotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We validated a pathogenic splicing variant in\n                      <jats:italic>PKD1<\/jats:italic>\n                      and successfully applied PGT-M to prevent disease transmission, resulting in an unaffected pregnancy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1850997","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T22:10:11Z","timestamp":1785967811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Functional validation of a PKD1 c.7489 + 5G&gt;A variant in an ADPKD family"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiong","family":"Pan","sequence":"first","affiliation":[{"name":"Genetic and Prenatal Diagnosis Center, Huai\u2019an Maternal and Child Health Care Hospital Affiliated to Yangzhou University","place":["Huai\u2019an, Jiangsu, China"]},{"name":"Genetic and Prenatal Diagnosis Center, The Huai\u2019an Maternity and Child Clinical College of Xuzhou Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Jiangsu College of Nursing","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, The First Affiliated Hospital with Nanjing Medical University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoulian","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, The First Affiliated Hospital with Nanjing Medical University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Li","sequence":"additional","affiliation":[{"name":"Genetic and Prenatal Diagnosis Center, Huai\u2019an Maternal and Child Health Care Hospital Affiliated to Yangzhou University","place":["Huai\u2019an, Jiangsu, China"]},{"name":"Genetic and Prenatal Diagnosis Center, The Huai\u2019an Maternity and Child Clinical College of Xuzhou Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandong","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, The First Affiliated Hospital with Nanjing Medical University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s13353-019-00493-z","article-title":"Correction to: splicing mutations in human genetic disorders: examples, detection, and confirmation","volume":"60","author":"Abramowicz","year":"2019","journal-title":"J. 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