{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:49:21Z","timestamp":1790833761055,"version":"4.1.0"},"reference-count":54,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>PHEX is the gene defective in X-linked hypophosphatemic rickets. In this study, analysis of PHEX revealed mutations in 22 hypophosphatemic rickets patients, including 16 of 28 patients in whom all 22 PHEX exons were studied. In 13 patients, in whom no PHEX mutation had been previously detected in 17 exons, the remaining 5 PHEX exons were analyzed and mutations found in 6 patients. Twenty different mutations were identified, including 16 mutations predicted to truncate PHEX and 4 missense mutations.<\/jats:p><jats:p>Phenotype analysis was performed on 31 hypophosphatemic rickets patients with PHEX mutations, including the 22 patients identified in this study, 9 patients previously identified, and affected family members. No correlation was found between the severity of disease and the type or location of the mutation. However, among patients with a family history of hypophosphatemic rickets, there was a trend toward more severe skeletal disease in patients with truncating mutations. Family members in more recent generations had a milder phenotype. Postpubertal males had a more severe dental phenotype. In conclusion, although identifying mutations in PHEX may have limited prognostic value, genetic testing may be useful for the early identification and treatment of affected individuals. Furthermore, this study suggests that other genes and environmental factors affect the severity of hypophosphatemic rickets.<\/jats:p>","DOI":"10.1210\/jcem.86.8.7761","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:07:29Z","timestamp":1389200849000},"page":"3889-3899","source":"Crossref","is-referenced-by-count":110,"title":["Mutational Analysis and Genotype-Phenotype Correlation of the PHEX Gene in X-Linked Hypophosphatemic Rickets"],"prefix":"10.1210","volume":"86","author":[{"given":"Ingrid A.","family":"Holm","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine (I.A.H.), Children\u2019s Hospital, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Cancer Genetics Department (A.E.N., B.G.R., R.S.M., D.J.M.), Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, Australia;"},{"name":"partment of Physiology and Institute for Biomedical Research (A.E.N., R.S.M.), University of Sydney, Sydney 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce G.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Cancer Genetics Department (A.E.N., B.G.R., R.S.M., D.J.M.), Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, Australia;"},{"name":"Department of Medicine (B.G.R., D.J.M.), University of Sydney, Sydney 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca S.","family":"Mason","sequence":"additional","affiliation":[{"name":"Cancer Genetics Department (A.E.N., B.G.R., R.S.M., D.J.M.), Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, Australia;"},{"name":"partment of Physiology and Institute for Biomedical Research (A.E.N., R.S.M.), University of Sydney, Sydney 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Cancer Genetics Department (A.E.N., B.G.R., R.S.M., D.J.M.), Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, Australia;"},{"name":"Department of Medicine (B.G.R., D.J.M.), University of Sydney, Sydney 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Cowell","sequence":"additional","affiliation":[{"name":"The New Children\u2019s Hospital (C.T.C.), Westmead 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Endocrinology) (T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520-8064"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071618254197200_R1","first-page":"3717","article-title":"Mendelian hypophosphatemias","author":"Rasmussen","year":"1995","journal-title":"In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw-Hill;"},{"key":"2020071618254197200_R2","first-page":"287","article-title":"Familial hypophosphatemic rickets showing autosomal dominant inheritance","volume":"VII","author":"Bianchine","year":"1971","journal-title":"Birth Defects Orig Artic Ser"},{"key":"2020071618254197200_R3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1210\/jcem.82.2.3765","article-title":"Autosomal dominant hypophosphatemic rickets\/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder.","volume":"82","author":"Econs","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618254197200_R4","first-page":"563","article-title":"[Scriver type autosomal hypophosphatemic rachitis: a family case].","volume":"42","author":"David","year":"1987","journal-title":"Pediatrie"},{"key":"2020071618254197200_R5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00005792-196503000-00001","article-title":"Studies in hypophosphatemic vitamin D-refractory osteomalacia in adults.","volume":"44","author":"Wilson","year":"1965","journal-title":"Medicine"},{"key":"2020071618254197200_R6","first-page":"290","article-title":"Growth disturbance in hereditary hypophosphatemia.","volume":"112","author":"Harrison","year":"1966","journal-title":"Am J Dis Child"},{"key":"2020071618254197200_R7","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1136\/adc.64.8.1209-a","article-title":"Autosomal recessive hypophosphataemia [letter]","volume":"64","author":"Baker","year":"1989","journal-title":"Arch Dis Child"},{"key":"2020071618254197200_R8","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/ajmg.1320350318","article-title":"Familial renal hypophosphatemia, minor facial anomalies, intracerebral calcifications, and non-rachitic bone changes: apparently new syndrome?","volume":"35","author":"Chitayat","year":"1990","journal-title":"Am J Med Genet"},{"key":"2020071618254197200_R9","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1302\/0301-620X.60B3.681423","article-title":"Hereditary hypophosphataemic rickets with autosomal recessive inheritance and severe osteosclerosis","volume":"60-B","author":"Perry","year":"1978","journal-title":"A report of two cases. J Bone Joint Surg Br"},{"key":"2020071618254197200_R10","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/S0140-6736(87)91407-3","article-title":"Renal hypophosphataemia has several mendelian forms [letter]","volume":"2","author":"Scriver","year":"1987","journal-title":"Lancet"},{"key":"2020071618254197200_R11","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1136\/adc.51.5.360","article-title":"Recessive hypophosphataemic rickets, and possible aetiology of the \u2018vitamin D-resistant\u2019 syndrome.","volume":"51","author":"Stamp","year":"1976","journal-title":"Arch Dis Child"},{"key":"2020071618254197200_R12","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1542\/peds.25.6.959","article-title":"\u201cSporadic\u201d hypophosphatemia and vitamin D-resistant rickets.","volume":"25","author":"Winters","year":"1960","journal-title":"Pediatrics"},{"key":"2020071618254197200_R13","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/ng1095-130","article-title":"A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets.","volume":"11","year":"1995","journal-title":"Nat Genet"},{"key":"2020071618254197200_R14","doi-asserted-by":"crossref","first-page":"7103","DOI":"10.1073\/pnas.86.18.7103","article-title":"Organization of the gene encoding common acute lymphoblast miniexons and separate 5\u2032 untranslated regions.","volume":"86","author":"D\u2019Adamio","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071618254197200_R15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/0092-8674(94)90425-1","article-title":"ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1","volume":"78","author":"Xu","year":"1994","journal-title":"Cell"},{"key":"2020071618254197200_R16","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.1073\/pnas.88.14.6353","article-title":"Molecular cloning and primary structure of Kell blood group protein","volume":"88","author":"Lee","year":"1991","journal-title":"Proc Natl Acad Sci USA."},{"key":"2020071618254197200_R17","first-page":"790","article-title":"Mutational analysis of the PEX gene in patients with X-linked hypophosphatemic rickets","volume":"60","author":"Holm","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2020071618254197200_R18","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"},{"key":"2020071618254197200_R19","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/hmg\/6.2.165","article-title":"Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia.","volume":"6","author":"Strom","year":"1997","journal-title":"Hum Mol Genet"},{"key":"2020071618254197200_R20","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"},{"key":"2020071618254197200_R21","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1359\/jbmr.1997.12.7.1009","article-title":"Cloning and sequencing of human PEX from a bone cDNA library: evidence for its developmental state-specific regulation in osteoblasts.","volume":"12","author":"Guo","year":"1997","journal-title":"J Bone Miner Res"},{"key":"2020071618254197200_R22","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1006\/bbrc.1997.6153","article-title":"Expression and cloning of the human X-linked hypophosphatemia gene cDNA.","volume":"231","author":"Grieff","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071618254197200_R23","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1172\/JCI119276","article-title":"Pex\/PEX tissue distribution and evidence for a deletion in the 3\u2032 region of the Pex gene in X-linked hypophosphatemic mice.","volume":"99","author":"Beck","year":"1997","journal-title":"J Clin Invest"},{"key":"2020071618254197200_R24","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1177\/002215549804600405","article-title":"Pex mRNA is localized in developing mouse osteoblasts and odontoblasts.","volume":"46","author":"Ruchon","year":"1998","journal-title":"J Histochem Cytochem"},{"key":"2020071618254197200_R25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1006\/geno.1996.0421","article-title":"cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone.","volume":"36","author":"Du","year":"1996","journal-title":"Genomics"},{"key":"2020071618254197200_R26","doi-asserted-by":"crossref","first-page":"13729","DOI":"10.1074\/jbc.273.22.13729","article-title":"Cloning of human PEX cDNA. Expression, subcellular localization, and endopeptidase activity.","volume":"273","author":"Lipman","year":"1998","journal-title":"J Biol Chem"},{"key":"2020071618254197200_R27","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/sj.ejhg.5200341","article-title":"Non-random distribution of mutations in the PHEX gene, and under-detected missense mutations at non-conserved residues.","volume":"7","author":"Filisetti","year":"1999","journal-title":"Eur J Hum Genet"},{"key":"2020071618254197200_R28","first-page":"3615","article-title":"Mutational analysis of PHEX gene in X-linked hypophosphatemia.","volume":"83","author":"Dixon","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618254197200_R29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0031-3955(05)70485-5","article-title":"New perspectives on the biology and treatment of X-linked hypophosphatemic rickets.","volume":"44","author":"Carpenter","year":"1997","journal-title":"Pediatr Clin North Am"},{"key":"2020071618254197200_R30","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1148\/radiology.171.2.2539609","article-title":"X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features.","volume":"171","author":"Hardy","year":"1989","journal-title":"Radiology"},{"key":"2020071618254197200_R31","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"},{"key":"2020071618254197200_R32","first-page":"434","article-title":"X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney.","volume":"46","author":"Shields","year":"1990","journal-title":"Am J Hum Genet"},{"key":"2020071618254197200_R33","first-page":"4075","article-title":"X-linked hypophosphatemia: a search for gender, race, anticipation, or parent of origin effects on disease expression in children.","volume":"81","author":"Whyte","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618254197200_R34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1017\/S0016672300031542","article-title":"Parental origin of mutant allele does not explain absence of gene dose in X-linked Hyp mice.","volume":"62","author":"Qiu","year":"1993","journal-title":"Genet Res"},{"key":"2020071618254197200_R35","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/jor.1100130107","article-title":"Femoral abnormalities and vitamin D metabolism in X-linked hypophosphatemic (Hyp and Gy) mice.","volume":"13","author":"Meyer Jr","year":"1995","journal-title":"J Orthop Res"},{"key":"2020071618254197200_R36","author":"Little","year":"1995"},{"key":"2020071618254197200_R37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1365-2796.1995.tb01208.x","article-title":"Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium.","volume":"238","author":"Mulligan","year":"1995","journal-title":"J Intern Med"},{"key":"2020071618254197200_R38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1214\/ss\/1177011454","article-title":"A survey of exact inference for contingency tables.","volume":"7","author":"Agresti","year":"1992","journal-title":"Stat Sci"},{"key":"2020071618254197200_R39","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/hmg\/7.3.507","article-title":"Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.","volume":"7","author":"Marsh","year":"1998","journal-title":"Hum Mol Genet"},{"key":"2020071618254197200_R40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/1098-1004(200007)16:1<1::AID-HUMU1>3.0.CO;2-J","article-title":"PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia.","volume":"16","author":"Sabbagh","year":"2000","journal-title":"Hum Mutat"},{"key":"2020071618254197200_R41","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s004399900092","article-title":"A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC.","volume":"105","author":"Gross","year":"1999","journal-title":"Hum Genet"},{"key":"2020071618254197200_R42","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1093\/hmg\/3.5.801","article-title":"Sensitivity of single-strand conformation polymorphism and heteroduplex method for mutation detection in the cystic fibrosis gene.","volume":"3","author":"Ravnik-Glavac","year":"1994","journal-title":"Hum Mol Genet"},{"key":"2020071618254197200_R43","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/(SICI)1098-1004(1997)10:1<65::AID-HUMU9>3.0.CO;2-L","article-title":"SSCP analysis: a blind sensitivity trial.","volume":"10","author":"Jordanova","year":"1997","journal-title":"Hum Mutat"},{"key":"2020071618254197200_R44","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/(SICI)1522-2683(19990101)20:6<1177::AID-ELPS1177>3.0.CO;2-2","article-title":"Single-strand conformation polymorphism and heteroduplex analysis for gel-based mutation detection.","volume":"20","author":"Nataraj","year":"1999","journal-title":"Electrophoresis"},{"key":"2020071618254197200_R45","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.","volume":"26","author":"White","year":"2000","journal-title":"Nat Genet"},{"key":"2020071618254197200_R46","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/BF00219180","article-title":"Three DNA markers for hypophosphataemic rickets.","volume":"89","author":"Rowe","year":"1992","journal-title":"Hum Genet"},{"key":"2020071618254197200_R47","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/S0021-9258(18)52423-6","article-title":"Evidence that both arginine 102 and arginine 747 are involved in substrate binding to neutral endopeptidase (EC 3.4.24.11).","volume":"266","author":"Beaumont","year":"1991","journal-title":"J Biol Chem"},{"key":"2020071618254197200_R48","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/BF01799618","article-title":"X-linked hypophosphataemia: a homologous phenotype in humans and mice with unusual organ-specific gene dosage.","volume":"15","author":"Scriver","year":"1992","journal-title":"J Inherit Metab Dis"},{"key":"2020071618254197200_R49","first-page":"43","article-title":"Scanning electron microscopic analysis of dentin in vitamin D-resistant rickets\u2013assessment of mineralization and correlation with clinical findings.","volume":"13","author":"Seeto","year":"1991","journal-title":"Pediatr Dent"},{"key":"2020071618254197200_R50","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1067\/moe.2000.107522","article-title":"Familial hypophosphatemic vitamin D-resistant rickets: dental findings and histologic study of teeth.","volume":"90","author":"Murayama","year":"2000","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"2020071618254197200_R51","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1046\/j.1365-263X.1998.00059.x","article-title":"Dental problems associated with hypophosphataemic vitamin D resistant rickets.","volume":"8","author":"Goodman","year":"1998","journal-title":"Int J Paediatr Dent"},{"key":"2020071618254197200_R52","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1136\/jmg.33.8.700","article-title":"X chromosome inactivation pattern in female carriers of X linked hypophosphataemic rickets.","volume":"33","author":"Orstavik","year":"1996","journal-title":"J Med Genet"},{"key":"2020071618254197200_R53","doi-asserted-by":"crossref","first-page":"14440","DOI":"10.1073\/pnas.96.25.14440","article-title":"A first-generation X-inactivation profile of the human X chromosome [see comments].","volume":"96","author":"Carrel","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071618254197200_R54","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0022-3476(95)70081-1","article-title":"Recurring oral giant cell lesion in a child with X-linked hypophosphatemic rickets: clinical manifestation of occult parathyroidism?","volume":"127","author":"Stratakis","year":"1995","journal-title":"J Pediatr"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/86\/8\/3889\/9168390\/jcem3889.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/86\/8\/3889\/9168390\/jcem3889.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:12:11Z","timestamp":1647907931000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/86\/8\/3889\/2849028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,1]]},"references-count":54,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.86.8.7761","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8,1]]}}}