{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:02:59Z","timestamp":1780473779529,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>SLC20A1<\/jats:italic>\n                    encodes the ubiquitously expressed phosphate transporter PiT1, a protein with roles extending beyond phosphate homeostasis to include regulation of proliferation, differentiation, apoptosis, and embryonic development. While heterozygous\n                    <jats:italic>SLC20A1<\/jats:italic>\n                    variants have been associated with urinary tract malformations, the impact of biallelic loss\u2010of\u2010function was unknown. We report the first human case of a biallelic homozygous predicted loss of function variant in\n                    <jats:italic>SLC20A1<\/jats:italic>\n                    (c.674_675delAA; p.K225TfsX34) in a child with multiple congenital anomalies including tetralogy of Fallot, unilateral renal agenesis, postaxial polydactyly, growth impairment, and developmental delay. PiT1 expression was decreased in fibroblasts of the proband. Transcriptome analysis of patient\u2010derived fibroblasts suggests significant dysregulation of pathways critical for organogenesis, including PI3K\u2013Akt, Wnt, MAPK, and BMP signaling. Population screening identified a carrier frequency of 1:432 among Ashkenazi Jewish individuals. Our findings expand the phenotypic spectrum of\n                    <jats:italic>SLC20A1<\/jats:italic>\n                    \u2010related disease and provide evidence that biallelic PiT1 deficiency causes a previously unrecognized multisystem developmental disorder.\n                  <\/jats:p>","DOI":"10.1111\/cge.70167","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:19:25Z","timestamp":1774858765000},"page":"64-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Homozygous Loss\u2010of\u2010Function Variant in\n                    <scp>\n                      <i>SLC20A1<\/i>\n                    <\/scp>\n                    Coding for Ubiquitous Phosphate Transporter\n                    <scp>PiT1<\/scp>\n                    Is Associated With Multiple Developmental Abnormalities"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8237-7386","authenticated-orcid":false,"given":"Eug\u00e9nie","family":"Koumakis","sequence":"first","affiliation":[{"name":"Paris Cit\u00e9 University, INSERM UMR 1163, Imagine Institute  Paris France"},{"name":"Rheumatology Department, Cochin Hospital AP\u2010HP Centre\u2010Paris University, Reference Center for Rare Genetic Bone Disorders\u2010Cochin\u2010Constitutive Site  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Huber","sequence":"additional","affiliation":[{"name":"Paris Cit\u00e9 University, INSERM UMR 1163, Imagine Institute  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Leroy","sequence":"additional","affiliation":[{"name":"INSERM UMRS1151 CNRS UMR8253 Institut Necker\u2010Enfants Malades (INEM) Universit\u00e9 Paris Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Parisot","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Women\u2010Mother\u2010Child Department Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis","family":"Gaudin","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery University Hospital of Vaud  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Zaidan","sequence":"additional","affiliation":[{"name":"Paris\u2010Saclay University, Le Kremlin\u2010Bic\u00eatre, Nephrology\u2010Transplantation Department Bic\u00eatre University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Cormier\u2010Daire","sequence":"additional","affiliation":[{"name":"Paris Cit\u00e9 University, INSERM UMR 1163, Imagine Institute  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Friedlander","sequence":"additional","affiliation":[{"name":"INSERM UMRS1151 CNRS UMR8253 Institut Necker\u2010Enfants Malades (INEM) Universit\u00e9 Paris Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Dor Yeshorim Director Genetic Research and Resources  New York 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