{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:21:16Z","timestamp":1761218476001,"version":"3.41.2"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>X\u2010linked hypophosphatemic rickets (XLHR) is a rare genetic disease, often delayed in diagnosis due to the low degree of suspicion and limited access to sophisticated diagnostic tools that confirm the diagnosis, such as genetic testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Through a cross\u2010sectional and observational study, 26 patients with a previously presumptive diagnosis of X\u2010linked hypophosphatemic rickets (based on clinical history, laboratory findings, and physical examination), were followed for approximately 12\u00a0months. During 12\u00a0months of follow\u2010up, only 16 patients underwent genetic testing and enrolled in the study. Previous data were analyzed, such as clinical history (e.g., gender, current age, age of clinical diagnosis, age of admission to hospital, family history, and previous orthopedic surgery), physical exam, imaging tests (e.g., radiological changes) and laboratory tests (e.g., tubular maximum reabsorption rate of phosphate to glomerular filtration rate, alkaline phosphatase, and phosphate levels) at the time of the patient\u2019s admission to IEDE and UFRJ, to corroborate and substantiate our research. These data were extracted from the medical records of the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 16 patients analyzed by molecular biology techniques, the new generation sequencing (NGS), using DNA samples from oral swabs, we obtained seven variants never previously described, which were verified by Sanger sequencing. Among the seven variants never previously described, the most common coding impact was the nonsense mutation. We found two frameshift, one intronic splicing variant, three nonsense, and one deletion splice junction loss. Among patients with new mutations who presented data in the medical record, 100% showed a reduction in TmP\/GFR (average of 1.98\u2009mg\/dl), the most sensitive laboratory parameter at the time of diagnosis, as well as serum phosphorus (100% had hypophosphatemia on arrival at the referral hospitals\u2013\u2013average of 2.4\u00a0mg\/dl and median 2.3\u00a0mg\/dl). We also performed NGS on three mothers of the patients with identified mutations. Among these mothers, only one tested negative for the mutation and no family history was reported as well. This mother had serum phosphate of 3.5\u00a0mg\/dl (normal range: 2.5\u20134.5\u00a0mg\/dl) at the time of genetic test collection. The others had a positive test, low serum phosphorus at the time of the molecular test, in addition to a positive family history.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study describes seven new variants in the <jats:italic>PHEX<\/jats:italic> gene and aims to increase the knowledge of the scientific community about the types of mutations involving this gene, increasing information on the genetic basis of this condition, enabling future considerations about genotype\u2013phenotype correlation, in addition to diagnosis accurate and early.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1941","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T07:44:30Z","timestamp":1649231070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["X\u2010linked hypophosphatemic rickets: Description of seven new variants in patients followed up in reference hospitals in Rio de Janeiro"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-5663","authenticated-orcid":false,"given":"Iara","family":"Sant\u2019 Ana","sequence":"first","affiliation":[{"name":"Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE)  Rio de Janeiro Brazil"},{"name":"Endocrinology Division Universidade Federal do Rio de Janeiro (UFRJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-4075","authenticated-orcid":false,"given":"Renato","family":"Torrini","sequence":"additional","affiliation":[{"name":"Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-5604","authenticated-orcid":false,"given":"Maria Caroline","family":"Alves Coelho","sequence":"additional","affiliation":[{"name":"Universidade do Estado do Rio de Janeiro (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-8084","authenticated-orcid":false,"given":"Joyce","family":"Cantoni","sequence":"additional","affiliation":[{"name":"Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6752-2880","authenticated-orcid":false,"given":"Miguel","family":"Madeira","sequence":"additional","affiliation":[{"name":"Endocrinology Division Universidade Federal do Rio de Janeiro (UFRJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8906-0189","authenticated-orcid":false,"given":"M\u00e1rcia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Medical Genetic Service, Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira Universidade Federal do Rio de Janeiro (UFRJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1711801"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2014-0250-CP"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.9.5372"},{"key":"e_1_2_11_5_1","unstructured":"Database THGM.PHEXmutationshttp:\/\/hgmd.cf.ac.uk\/ac\/genr.php?gene=PHEX"},{"issue":"10","key":"e_1_2_11_6_1","first-page":"3615","article-title":"Mutational analysis of PHEX gene in X\u2010linked hypophosphatemia","volume":"83","author":"Dixon P. 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