{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:08:12Z","timestamp":1774645692356,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T00:00:00Z","timestamp":1404691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"STARS (Students and Teachers as Research Scientists)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Heritable forms of hypophosphatemic rickets (HR) include X-linked dominant (XLH), autosomal recessive, and autosomal dominant HR (from deactivating mutations in PHEX, DMP1 or ENPP1, and activating mutations in FGF23, respectively). Over 30 years, we have cared for 284 children with HR. For those 72 deemed sporadic XLH, we preliminarily reported mutation analysis for 30 subjects. Eleven had PHEX mutations. However, the remaining 19 lacked readily identifiable defects in PHEX, DMP1, or FGF23. In 2008, a novel single-base change near the polyadenylation (pA) signal in the 3\u2032-UTR of PHEX was identified in XLH by other investigators. This c.*231A\u2009&amp;gt;\u2009G mutation is 3-bp upstream of the putative pA signal (AATAAA) in PHEX. Accordingly, we investigated whether this 3\u2032-UTR defect accounted for HR in any of these 19 sporadic XLH patients. PCR amplification and sequencing of their 3\u2032-UTR region showed the c.*231A\u2009&amp;gt;\u2009G mutation in four unrelated boys. Then, among an additional 22 of our 72 \u201csporadic\u201d XLH patients, one boy and one girl were found to have the 3\u2032-UTR defect, totaling six patients. Among these 52 sporadic XLH patients with PHEX analysis, 36 were girls and 16 were boys; ie, a \u223c2:1 gender ratio consistent with XLH. However, finding five boys and only one girl with this 3\u2032-UTR mutation presented an unexplained gender bias (p\u2009=\u20090.02). Haplotyping for the five boys, all reportedly unrelated, showed a common core haplotype suggesting a founder. Five of their six mothers had been studied clinically and biochemically (three radiologically). Remarkably, the seemingly unaffected mothers of four of these boys carried the 3\u2032-UTR mutation. These healthy women had normal height, straight limbs, lacked the radiographic presentation of XLH, and showed normal or slight decreases in fasting serum Pi levels and\/or TmP\/GFR. Hence, PHEX c.*231A\u2009&amp;gt;\u2009G can masquerade as sporadic or X-linked recessive HR. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2307","type":"journal-article","created":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T04:23:11Z","timestamp":1404706991000},"page":"137-143","source":"Crossref","is-referenced-by-count":22,"title":["<i>PHEX<\/i> 3\u2032-UTR c.*231A&amp;gt;G Near The Polyadenylation Signal Is a Relatively Common, Mild, American Mutation That Masquerades as Sporadic or X-Linked Recessive Hypophosphatemic Rickets"],"prefix":"10.1093","volume":"30","author":[{"given":"Steven","family":"Mumm","sequence":"first","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"},{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Huskey","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Cajic","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Wollberg","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"},{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine L","family":"Madson","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Wenkert","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H","family":"McAlister","sequence":"additional","affiliation":[{"name":"Department of Pediatric RadiologyMallinckrodt Institute of Radiology, St. Louis Children's Hospital, Washington University School of MedicineSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary S","family":"Gottesman","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P","family":"Whyte","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMOUSA"},{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMOUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,7,7]]},"reference":[{"key":"2024020319202325900_jbmr2307-bib-0001","first-page":"529","article-title":"Rickets resistant to vitamin D therapy","volume":"54","author":"Albright","year":"1937","journal-title":"Am J Dis 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Genet."},{"key":"2024020319202325900_jbmr2307-bib-0006","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/ng1868","article-title":"DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis","volume":"38","author":"Lorenz-Depiereux","year":"2006","journal-title":"Nat Genet."},{"issue":"2","key":"2024020319202325900_jbmr2307-bib-0007","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ajhg.2010.01.010","article-title":"Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene","volume":"86","author":"Levy-Litan","year":"2010","journal-title":"Am J Hum Genet."},{"issue":"2","key":"2024020319202325900_jbmr2307-bib-0008","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2010.01.006","article-title":"Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive 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Nat Genet."},{"key":"2024020319202325900_jbmr2307-bib-0010","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/379445a0","article-title":"A common molecular basis for three inherited kidney stone diseases","volume":"379","author":"Lloyd","year":"1996","journal-title":"Nature."},{"key":"2024020319202325900_jbmr2307-bib-0011","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1148\/radiology.171.2.2539609","article-title":"X\u2013linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features","volume":"171","author":"Hardy","year":"1989","journal-title":"Radiology."},{"key":"2024020319202325900_jbmr2307-bib-0012","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/00005792-198911000-00002","article-title":"X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults","volume":"68","author":"Reid","year":"1989","journal-title":"Medicine 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can identify genomic disruptions of phex causing X-linked hypophosphatemic rickets","volume":"26","author":"Mumm","year":"2011","journal-title":"J Bone Miner Res."},{"issue":"4","key":"2024020319202325900_jbmr2307-bib-0017","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/hmg\/6.4.539","article-title":"Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)","volume":"6","author":"Rowe","year":"1997","journal-title":"Hum Mol Genet."},{"issue":"6","key":"2024020319202325900_jbmr2307-bib-0018","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1101\/gr.7.6.573","article-title":"Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets","volume":"7","author":"Francis","year":"1997","journal-title":"Genome Res."},{"issue":"8","key":"2024020319202325900_jbmr2307-bib-0019","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1210\/jcem.86.8.7761","article-title":"Mutational analysis 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children","volume":"81","author":"Whyte","year":"1996","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020319202325900_jbmr2307-bib-0028","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00223-013-9736-4","article-title":"Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia","volume":"93","author":"Ichikawa","year":"2013","journal-title":"Calcif Tissue Int."}],"container-title":["Journal of Bone and Mineral 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