{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:02:58Z","timestamp":1780473778689,"version":"3.54.1"},"reference-count":9,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004351","name":"Sultan Qaboos University","doi-asserted-by":"publisher","award":["IG\/MED\/GENE\/19\/01"],"award-info":[{"award-number":["IG\/MED\/GENE\/19\/01"]}],"id":[{"id":"10.13039\/501100004351","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004351","name":"Sultan Qaboos University","doi-asserted-by":"publisher","award":["IG\/MED\/GENT\/21\/01"],"award-info":[{"award-number":["IG\/MED\/GENT\/21\/01"]}],"id":[{"id":"10.13039\/501100004351","id-type":"DOI","asserted-by":"publisher"}]}],"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>XPR1<\/jats:italic>\n                    encodes the only known phosphate exporter in human cells and regulates the export of inorganic phosphate (Pi). To date, heterozygous pathogenic variants have been reported to be associated with autosomal\u2010dominant idiopathic basal ganglia calcification\u20106 (IBGC6; MIM: 616413). We collate clinical information on individuals with biallelic\n                    <jats:italic>XPR1<\/jats:italic>\n                    variants and use in silico and cell\u2010based studies to evaluate pathogenicity. Four consanguineous families have been documented, with a severe neonatal phenotype presenting with persistent pulmonary hypertension, chronic lung disease, cardiomyopathy, and hypophosphatemia. Affected individuals exhibit microcephaly, intracranial calcifications, and profound neurodevelopmental impairment; the prognosis is generally poor. Exome and Sanger sequencing confirmed segregation with homozygosity for a rare, likely deleterious, biallelic\n                    <jats:italic>XPR1<\/jats:italic>\n                    variant NM_004736.4: c.1811G&gt;A: p.Arg604Gln. Analysis of primary cell lines showed stable expression of the XPR1 protein. In silico structural analysis supported the variant's deleterious nature. Published mutagenesis studies demonstrate that mutations at the arginine residue (Arg604) within the second putative Pi coordination site substantially impair Pi export in functional flux assays. This study establishes a link between a novel severe neonatal disease and specific biallelic variants in\n                    <jats:italic>XPR1<\/jats:italic>\n                    that result in a loss\u2010of\u2010function phenotype.\n                  <\/jats:p>","DOI":"10.1111\/cge.70161","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T09:50:59Z","timestamp":1773654659000},"page":"102-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic\n                    <scp>\n                      <i>XPR1<\/i>\n                    <\/scp>\n                    Variants Are Linked to Brain Calcifications, Developmental Delay, Hypophosphatemia, and Cardiopulmonary Phenotype"],"prefix":"10.1111","volume":"110","author":[{"given":"Fakhriya","family":"Al\u2010Azri","sequence":"first","affiliation":[{"name":"Department of Genetics, College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Al\u2010Rashdi","sequence":"additional","affiliation":[{"name":"Department of Genetics, College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathiya","family":"Al\u2010Murshedi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Sultan Qaboos University Hospital University Medical City  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada A.","family":"Otaify","sequence":"additional","affiliation":[{"name":"Department of Genetics, Sultan Qaboos University Hospital University Medical City  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-7935","authenticated-orcid":false,"given":"Tariq","family":"Al\u2010Jabry","sequence":"additional","affiliation":[{"name":"Department of Genetics, College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adila","family":"Al\u2010Kindi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Sultan Qaboos University Hospital University Medical City  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobia Ahsan","family":"Halim","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Centre University of Nizwa  Nizwa Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-5942","authenticated-orcid":false,"given":"Ahmed","family":"Al\u2010Harrasi","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Centre University of Nizwa  Nizwa Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-8887","authenticated-orcid":false,"given":"Almundher","family":"Al\u2010Maawali","sequence":"additional","affiliation":[{"name":"Department of Genetics, College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"},{"name":"Department of Genetics, Sultan Qaboos University Hospital University Medical City  Muscat Oman"},{"name":"Medical Research Center Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.05.035"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3289"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201055995\u20108"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp3252"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007852\u20109"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201043255\u2010x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201058195\u20106"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22220"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016070726\/\u2010\/DCSUPPLEMENTAL"}],"container-title":["Clinical 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History"}},{"value":"2026-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}