{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:46:28Z","timestamp":1770144388526,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Society of Nephrology"},{"name":"AstraZeneca"},{"name":"Alexion"},{"name":"Chiesi"},{"name":"Alnylam"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Podocalyxin is a sialoprotein mainly expressed in the kidney cortex and lung tissue, which has been described as a component of the podocyte glycocalyx. This protein promotes the reorganization of the podocyte cytoskeleton, as well as the morphogenesis and differentiation of nascent podocytes, actively participating in glomerular filtration. Previous research has suggested that PODXL haploinsufficiency leads to podocytopathy with development of focal segmental glomerulosclerosis, a disorder that has been demonstrated in Podxl-deficient animal models and proposed as a primary cause in human families affected by this condition. However, only a few families have been reported, which limits the understanding about the spectrum of phenotype and prognosis of the disease. Methods: We performed high-throughput sequencing in a cohort of young adults with CKD, describing the clinical scenario of those who harbored truncating variants in the PODXL gene and testing the families for detected variants. Results: The PODXL gene exhibited a slight deviation in loss intolerance probability and moderate deviation in the observed\/expected ratio of variation, which is typically observed in dominant genes with age-dependent incomplete penetrance or variable expression. We reported four novel truncating variants in the PODXL gene, along with a collection of previously published monoallelic truncating variants. Conclusions: These findings further support evidence about genetic defects in the PODXL gene associated with a new molecular entity of podocytopathy with adult onset. Additionally, the nucleotide sequence of PODXL contains particularities that require careful analysis to interpret the effect of the variants detected in this gene.<\/jats:p>","DOI":"10.3390\/genes16040464","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T05:11:16Z","timestamp":1744953076000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Truncating Variants in PODXL Represent a New Entity to Be Explored Among Podocytopathies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-6823","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Garc\u00eda-Aznar","sequence":"first","affiliation":[{"name":"Clinical Area of Genetic Diagnostic in Nephrology, Healthincode, 15008 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Lara","family":"Besada-Cerecedo","sequence":"additional","affiliation":[{"name":"Clinical Area of Genetic Diagnostic in Nephrology, Healthincode, 15008 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-1953","authenticated-orcid":false,"given":"Cristina","family":"Castro-Alonso","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Doctor Peset University Hospital, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milagros","family":"Sierra Carpio","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitario San Pedro, 26006 Logro\u00f1o, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miquel","family":"Blasco","sequence":"additional","affiliation":[{"name":"Nephrology and Kidney Transplant Department, National Reference Center for Complex Glomerular Diseases (CSUR), Hospital Cl\u00ednic, Barcelona University, 08036 Barcelona, Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-1929","authenticated-orcid":false,"given":"Borja","family":"Quiroga","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitario de la Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"\u010cervienka","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital El Bierzo, 24404 Ponferrada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-4291","authenticated-orcid":false,"given":"Ricardo","family":"Mouzo","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital El Bierzo, 24404 Ponferrada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-2332","authenticated-orcid":false,"given":"Roser","family":"Torra","sequence":"additional","affiliation":[{"name":"Nephrology Department, Fundaci\u00f3 Puigvert, 08025 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension Department, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz UAM, 28040 Madrid, Spain"},{"name":"Medicine Department, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-9228","authenticated-orcid":false,"given":"Patricia","family":"de Sequera","sequence":"additional","affiliation":[{"name":"Nephrology Department, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"},{"name":"Medicine Department, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1083\/jcb.98.4.1591","article-title":"Identification and characterization of podocalyxin\u2014The major sialoprotein of the renal glomerular epithelial cell","volume":"98","author":"Kerjaschki","year":"1984","journal-title":"J. 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