{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:49:50Z","timestamp":1790833790774,"version":"4.1.0"},"reference-count":28,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. Sequencing of the ALPL gene produced evidence of two distinct missense mutations, E174K (c.571G&amp;gt;A), of maternal origin, and a de novo mutation, M45I (c.186G&amp;gt;C). The study of various microsatellite polymorphisms ruled out false paternity and therefore confirmed that M45I occurred de novo in the paternal germline or in the early development of the patient. Site-directed mutagenesis showed that M45I results in the absence of in vitro alkaline phosphatase activity, suggesting that the mutation is a severe allele. In conclusion, childhood hypophosphatasia in this patient is the result of compound heterozygosity for the moderate mutation E174K and a novel severe de novo mutation M45I.<\/jats:p>","DOI":"10.1210\/jc.2004-1456","type":"journal-article","created":{"date-parts":[[2005,4,6]],"date-time":"2005-04-06T23:32:44Z","timestamp":1112830364000},"page":"2436-2439","source":"Crossref","is-referenced-by-count":27,"title":["Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene"],"prefix":"10.1210","volume":"90","author":[{"given":"A.","family":"Taillandier","sequence":"first","affiliation":[{"name":"Laboratoire SESEP, Universite\u0301 de Versailles-Saint Quentin en Yvelines (A.T., E.M.), F-78035 Versailles, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.-L.","family":"Sallinen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Tampere University Hospital (S.-L.S.), Tampere, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Brun-Heath","sequence":"additional","affiliation":[{"name":"Equipe Structure-Fonction et Ge\u0301ne\u0301tique, UA 2493, Centre Hospitalier Universitaire Paris Ile de France Ouest, Universite\u0301 de Versailles-Saint Quentin en Yvelines (I.B.-H., P.D.M., J.-L.S., E.M.), Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"De Mazancourt","sequence":"additional","affiliation":[{"name":"Equipe Structure-Fonction et Ge\u0301ne\u0301tique, UA 2493, Centre Hospitalier Universitaire Paris Ile de France Ouest, Universite\u0301 de Versailles-Saint Quentin en Yvelines (I.B.-H., P.D.M., J.-L.S., E.M.), Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.-L.","family":"Serre","sequence":"additional","affiliation":[{"name":"Equipe Structure-Fonction et Ge\u0301ne\u0301tique, UA 2493, Centre Hospitalier Universitaire Paris Ile de France Ouest, Universite\u0301 de Versailles-Saint Quentin en Yvelines (I.B.-H., P.D.M., J.-L.S., E.M.), Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Mornet","sequence":"additional","affiliation":[{"name":"Equipe Structure-Fonction et Ge\u0301ne\u0301tique, UA 2493, Centre Hospitalier Universitaire Paris Ile de France Ouest, Universite\u0301 de Versailles-Saint Quentin en Yvelines (I.B.-H., P.D.M., J.-L.S., E.M.), Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071615461510800_R1","first-page":"439","article-title":"Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization.","volume":"15","author":"Whyte","year":"1994","journal-title":"Endocr Rev"},{"key":"2020071615461510800_R2","first-page":"651","article-title":"Hypophosphatasia","author":"Cole","year":"2003","journal-title":"In: Glorieux FH, Pettifor JM, Juppner H, eds. Pediatric bone: biology and disease, chapt 27. Amsterdam: Academic Press;"},{"key":"2020071615461510800_R3","first-page":"213","article-title":"Clinical, laboratory, and genetic investigations of hypophosphatasia: support for autosomal dominant inheritance with homozygous lethality.","volume":"3","author":"Eastman","year":"1983","journal-title":"J Craniofac Genet Dev Biol"},{"key":"2020071615461510800_R4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/BF01716257","article-title":"Adult hypophosphatasia without apparent skeletal disease: \u201condotohypophosphatasia\u201d in four heterozygote members of a family.","volume":"62","author":"Eberic","year":"1984","journal-title":"Klin Wochenschr"},{"key":"2020071615461510800_R5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1034\/j.1600-0722.2000.108003189.x","article-title":"Case report of a family with dominant hypophosphatasia.","volume":"108","author":"Hu","year":"2000","journal-title":"Eur J Oral Sci"},{"key":"2020071615461510800_R6","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1136\/jmg.40.8.605","article-title":"Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene.","volume":"40","author":"Herasse","year":"2003","journal-title":"J Med Genet"},{"key":"2020071615461510800_R7","first-page":"286","article-title":"Infantile hypophosphatasia localization within chromosome region 1p36.1.1-34 and prenatal diagnosis using linked DNA markers.","volume":"46","author":"Greenberg","year":"1990","journal-title":"Am J Hum Genet"},{"key":"2020071615461510800_R8","doi-asserted-by":"crossref","first-page":"12002","DOI":"10.1016\/S0021-9258(18)37885-2","article-title":"Structure of the human liver\/bone\/kidney alkaline phosphatase gene.","volume":"263","author":"Weiss","year":"1988","journal-title":"J Biol Chem"},{"key":"2020071615461510800_R9","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1073\/pnas.85.20.7666","article-title":"A missense mutation in the liver\/bone\/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia.","volume":"85","author":"Weiss","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071615461510800_R10","doi-asserted-by":"crossref","first-page":"9924","DOI":"10.1073\/pnas.89.20.9924","article-title":"Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia.","volume":"89","author":"Henthorn","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071615461510800_R11","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1093\/hmg\/3.9.1683","article-title":"Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia.","volume":"3","author":"Orimo","year":"1994","journal-title":"Hum Mol Genet"},{"key":"2020071615461510800_R12","first-page":"4458","article-title":"Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia.","volume":"81","author":"Ozono","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615461510800_R13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1006\/geno.1997.4733","article-title":"Detection of deletion 1154\u20131156 hypophosphatasia mutation using TNSALP exon amplification.","volume":"42","author":"Orimo","year":"1997","journal-title":"Genomics"},{"key":"2020071615461510800_R14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1006\/bbrc.1998.8674","article-title":"Intracellular retention and degradation of tissue-nonspecific alkaline phosphatase with a Gly317Asp substitution associated with lethal hypophosphatasia.","volume":"246","author":"Fukushi","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"issue":"Suppl 1","key":"2020071615461510800_R15","first-page":"S263","article-title":"Hypophosphatasia: identification of five novel missense mutations (G507A, G705A, A748G, T1155C, G1320A) in the tissue-nonspecific alkaline phosphatase gene among Japanese patients","volume":"Mutat","author":"Goseki-Sone","year":"1998","journal-title":"Hum"},{"key":"2020071615461510800_R16","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s100380050061","article-title":"A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia.","volume":"43","author":"Sugimoto","year":"1998","journal-title":"J Hum Genet"},{"key":"2020071615461510800_R17","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/sj.ejhg.5200190","article-title":"Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia.","volume":"6","author":"Mornet","year":"1998","journal-title":"Eur J Hum Genet"},{"key":"2020071615461510800_R18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/(SICI)1098-1004(1999)13:2<171::AID-HUMU16>3.0.CO;2-T","article-title":"Characterization of eleven novel mutations (M45L, R119H, 544delG, G145 V, H154Y, C184Y, D289 V, 862+5A, 1172delC, R411X, E459 K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia.","volume":"13","author":"Taillandier","year":"1999","journal-title":"Hum Mutat"},{"key":"2020071615461510800_R19","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/hmg\/8.6.1039","article-title":"Correlations of genotype and phenotype in hypophosphatasia.","volume":"8","author":"Zurutuza","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2020071615461510800_R20","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s004310051290","article-title":"Severe hypercalcaemia and respiratory insufficiency associated with infantile hypophosphatasia caused by two novel mutations of the tissue-nonspecific alkaline phosphatase gene.","volume":"159","author":"Mochizuki","year":"2000","journal-title":"Eur J Pediatr"},{"key":"2020071615461510800_R21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/(SICI)1098-1004(200003)15:3<293::AID-HUMU11>3.0.CO;2-Q","article-title":"Fifteen new mutations (-195T, L-12X, 298\u20132G, T117 N, A159T, R229S, 997+2A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia.","volume":"15","author":"Taillandier","year":"2000","journal-title":"Hum Mutat"},{"key":"2020071615461510800_R22","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1359\/jbmr.2001.16.12.2313","article-title":"Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia.","volume":"16","author":"Orimo","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2020071615461510800_R23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1034\/j.1601-0825.2001.00740.x","article-title":"A novel point mutation (C571T) in the tissue-non-specific alkaline phosphatase gene in a case of adult-type hypophosphatasia.","volume":"7","author":"Watanabe","year":"2001","journal-title":"Oral Dis"},{"key":"2020071615461510800_R24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/humu.1154","article-title":"Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia.","volume":"18","author":"Taillandier","year":"2001","journal-title":"Hum Mutat"},{"key":"2020071615461510800_R25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1006\/mgme.2001.3283","article-title":"Denaturing gradient gel electrophoresis analysis of the tissue nonspecific alkaline phosphatase isoenzyme gene in hypophosphatasia.","volume":"75","author":"Mumm","year":"2002","journal-title":"Mol Genet Metab"},{"key":"2020071615461510800_R26","doi-asserted-by":"crossref","first-page":"31171","DOI":"10.1074\/jbc.M102788200","article-title":"Structural evidence for a functional role of human tissue non-specific alkaline phosphatase in bone mineralisation.","volume":"276","author":"Mornet","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071615461510800_R27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/(SICI)1098-1004(200004)15:4<309::AID-HUMU2>3.0.CO;2-C","article-title":"Hypophosphatasia: the mutations of the tissue-nonspecific alkaline phosphatase gene.","volume":"15","author":"Mornet","year":"2000","journal-title":"Hum Mutat"},{"key":"2020071615461510800_R28","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/sj.ejhg.5200857","article-title":"Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients.","volume":"10","author":"Herasse","year":"2002","journal-title":"Eur J Hum Genet"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/4\/2436\/10775713\/jcem2436.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/4\/2436\/10775713\/jcem2436.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T03:06:49Z","timestamp":1625713609000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/90\/4\/2436\/2836980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,1]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2004-1456","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,1]]}}}