{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:55:25Z","timestamp":1785477325604,"version":"3.56.0"},"reference-count":22,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,19]],"date-time":"2023-02-19T00:00:00Z","timestamp":1676764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Il Sogno di Stefano"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>PAX2 is a transcription factor expressed during embryogenesis in the eye, ear, CNS, and genitourinary tract, and is one of the major regulators of kidney development. Mutations in this gene are associated with papillorenal syndrome (PAPRS), a genetic condition characterized by optic nerve dysplasia and renal hypo\/dysplasia. In the last 28 years, many cohort studies and case reports highlighted PAX2\u2019s involvement in a large spectrum of kidney malformations and diseases, with or without eye abnormalities, defining the phenotypes associated with PAX2 variants as \u201cPAX2-related disorders\u201d. Here, we reported two new sequence variations and reviewed PAX2 mutations annotated on the Leiden Open Variation Database 3.0. DNA was extracted from the peripheral blood of 53 pediatric patients with congenital abnormalities of the kidney and urinary tract (CAKUT). PAX2 gene-coding exonic and flanking intronic regions were sequenced with Sanger technology. Two unrelated patients and two twins carrying one known and two unknown PAX2 variations were observed. The frequency of PAX2-related disorders in this cohort was 5.8%, considering all CAKUT phenotypes (16.7% in the PAPRS phenotype and 2.5% in non-syndromic CAKUT). Although PAX2 mutations have a higher frequency in patients with PAPRS or non-syndromic renal hypoplasia, from the review of variants reported to date in LOVD3, PAX2-related disorders are detected in pediatric patients with other CAKUT phenotypes. In our study, only one patient had a CAKUT without an ocular phenotype, but his twin had both renal and ocular involvement, confirming the extreme inter- and intrafamilial phenotypic variability.<\/jats:p>","DOI":"10.3390\/ijms24044165","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T04:28:57Z","timestamp":1676867337000},"page":"4165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PAX2 and CAKUT Phenotypes: Report on Two New Variants and a Review of Mutations from the Leiden Open Variation Database"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-1502","authenticated-orcid":false,"given":"Susanna","family":"Negrisolo","sequence":"first","affiliation":[{"name":"Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women\u2019s and Children\u2019s Health, University of Padova, 35127 Padua, Italy"},{"name":"Pediatric Research Institute \u201cIRP Citt\u00e0 della Speranza\u201d, 35127 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-6376","authenticated-orcid":false,"given":"Elisa","family":"Benetti","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women\u2019s and Children\u2019s Health, University of Padova, 35127 Padua, Italy"},{"name":"Pediatric Research Institute \u201cIRP Citt\u00e0 della Speranza\u201d, 35127 Padua, Italy"},{"name":"Pediatric Nephrology, Department of Women\u2019s and Children\u2019s Health, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s00467-010-1749-x","article-title":"Patterning and Early Cell Lineage Decisions in the Developing Kidney: The Role of Pax Genes","volume":"26","author":"Dressler","year":"2011","journal-title":"Pediatr. 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