{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:02:03Z","timestamp":1774645323729,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Lenz-Majewski hyperostotic dwarfism (LMHD) is an ultra-rare Mendelian craniotubular dysostosis that causes skeletal dysmorphism and widely distributed osteosclerosis. Biochemical and histopathological characterization of the bone disease is incomplete and nonexistent, respectively. In 2014, a publication concerning five unrelated patients with LMHD disclosed that all carried one of three heterozygous missense mutations in PTDSS1 encoding phosphatidylserine synthase 1 (PSS1). PSS1 promotes the biosynthesis of phosphatidylserine (PTDS), which is a functional constituent of lipid bilayers. In vitro, these PTDSS1 mutations were gain-of-function and increased PTDS production. Notably, PTDS binds calcium within matrix vesicles to engender hydroxyapatite crystal formation, and may enhance mesenchymal stem cell differentiation leading to osteogenesis. We report an infant girl with LMHD and a novel heterozygous missense mutation (c.829T&amp;gt;C, p.Trp277Arg) within PTDSS1. Bone turnover markers suggested that her osteosclerosis resulted from accelerated formation with an unremarkable rate of resorption. Urinary amino acid quantitation revealed a greater than sixfold elevation of phosphoserine. Our findings affirm that PTDSS1 defects cause LMHD and support enhanced biosynthesis of PTDS in the pathogenesis of LMHD. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2398","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T07:46:52Z","timestamp":1414828012000},"page":"606-614","source":"Crossref","is-referenced-by-count":23,"title":["Lenz-Majewski Hyperostotic Dwarfism with Hyperphosphoserinuria from a Novel Mutation in <i>PTDSS1<\/i> Encoding Phosphatidylserine Synthase 1"],"prefix":"10.1093","volume":"30","author":[{"given":"Michael P","family":"Whyte","sequence":"first","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMO"},{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Blythe","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H","family":"McAlister","sequence":"additional","affiliation":[{"name":"Department of Pediatric RadiologyMallinckrodt Institute of Radiology at St. Louis Children's HospitalWashington University School of MedicineSt. LouisMO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela R","family":"Nenninger","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinieth N","family":"Bijanki","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Mumm","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral DiseasesWashington University School of Medicine at Barnes-Jewish HospitalSt. LouisMO"},{"name":"Center for Metabolic Bone Disease and Molecular ResearchShriners Hospital for ChildrenSt. LouisMO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,11,1]]},"reference":[{"key":"2024020319174135900_jbmr2398-bib-0001","first-page":"528","volume-title":"Bone dysplasias: an atlas of genetic disorders of skeletal development","author":"Spranger","year":"2002","edition":"2nd ed"},{"key":"2024020319174135900_jbmr2398-bib-0002","author":"Online Mendelian Inheritance"},{"key":"2024020319174135900_jbmr2398-bib-0003","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng.2829","article-title":"Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome","volume":"46","author":"Sousa","year":"2014","journal-title":"Nat Genet."},{"key":"2024020319174135900_jbmr2398-bib-0004","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1074\/jbc.M707653200","article-title":"Analysis and molecular modeling of the formation, structure, and activity of the phosphatidylserine-calcium-phosphate complex associated with biomineralization","volume":"283","author":"Wu","year":"2008","journal-title":"J Biol Chem"},{"key":"2024020319174135900_jbmr2398-bib-0005","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.msec.2013.01.005","article-title":"Phosphatidylserine enhances osteogenic differentiation in human mesenchymal stem cells via ERK signal pathways","volume":"33","author":"Xu","year":"2013","journal-title":"Mater Sci Eng C Mater Biol Appl"},{"key":"2024020319174135900_jbmr2398-bib-0006","first-page":"133","article-title":"A generalized disorder of the connective tissues with progeria, choanal atresia, symphalangism, hypoplasia of dentine and craniodiaphyseal hyperostosis","volume":"10","author":"Lenz","year":"1974","journal-title":"Birth Defects Orig Art Ser"},{"key":"2024020319174135900_jbmr2398-bib-0007","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/1096-8628(20000814)93:4<335::AID-AJMG14>3.0.CO;2-5","article-title":"Lenz-Majewski hyperostotic dwarfism: reexamination of the original patient","volume":"93","author":"Majewski","year":"2000","journal-title":"Am J Med Genet"},{"key":"2024020319174135900_jbmr2398-bib-0008","first-page":"22","article-title":"Craniodiaphyseal dysplasia, a disease or group of diseases","volume":"25","author":"Macpherson","year":"1974","journal-title":"J Can Radiol"},{"key":"2024020319174135900_jbmr2398-bib-0009","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/0030-4220(69)90026-7","article-title":"Multiple congenital abnormalities with diaphyseal dysplasia (Camurati-Engelmann's Syndrome)","volume":"27","author":"Braham","year":"1969","journal-title":"Oral Surg"},{"key":"2024020319174135900_jbmr2398-bib-0010","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0022-3476(77)81311-5","article-title":"The Lenz-Majewski hyperostotic dwarfism. A syndrome of multiple congenital anomalies, mental retardation, and progressive skeletal sclerosis","volume":"91","author":"Robinow","year":"1977","journal-title":"J Pediatr"},{"key":"2024020319174135900_jbmr2398-bib-0011","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1148\/radiology.149.1.6611917","article-title":"Lenz-Majewski syndrome","volume":"149","author":"Gorlin","year":"1983","journal-title":"Radiology"},{"key":"2024020319174135900_jbmr2398-bib-0012","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/(SICI)1096-8628(20000320)91:3<198::AID-AJMG8>3.0.CO;2-4","article-title":"Dysgenesis of corpus callosum in Lenz-Majewski hyperostotic dwarfism","volume":"91","author":"Saraiva","year":"2000","journal-title":"Am J Med Genet."},{"key":"2024020319174135900_jbmr2398-bib-0013","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/(SICI)1096-8628(19970711)71:1<87::AID-AJMG16>3.0.CO;2-R","article-title":"Craniotubular dysplasia with severe postnatal growth retardation, mental retardation, ectodermal dysplasia, and loose skin: Lenz-Majewski-like syndrome","volume":"71","author":"Nishimura","year":"1997","journal-title":"Am J Med Genet"},{"key":"2024020319174135900_jbmr2398-bib-0014","first-page":"115","article-title":"Cutis laxa, skeletal anomalies, and ambiguous genitalia","volume":"127","author":"Kaye","year":"1974","journal-title":"Am J Dis Child."},{"key":"2024020319174135900_jbmr2398-bib-0015","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/ajmg.1320320407","article-title":"Skeletal dysplasia syndrome with progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes: a variant example of the Lenz-Majewski syndrome","volume":"32","author":"Chrzanowska","year":"1989","journal-title":"Am J Med Genet"},{"key":"2024020319174135900_jbmr2398-bib-0016","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/s10038-007-0165-y","article-title":"A Japanese patient with a mild Lenz-Majewski syndrome","volume":"52","author":"Dateki","year":"2007","journal-title":"J Hum Genet"},{"key":"2024020319174135900_jbmr2398-bib-0017","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/01.mcd.0000127468.11641.b7","article-title":"Expanding the phenotypic spectrum of Lenz-Majewski syndrome: facial palsy, cleft palate and hydrocephalus","volume":"13","author":"Wattanasirichaigoon","year":"2004","journal-title":"Clin Dysmorphol"},{"key":"2024020319174135900_jbmr2398-bib-0018","volume-title":"National Research Council. Dietary reference intakes: the essential guide to nutrient requirements","author":"Otten","year":"2006"},{"key":"2024020319174135900_jbmr2398-bib-0019","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1002\/jbmr.5650111010","article-title":"Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders","volume":"11","author":"Whyte","year":"1996","journal-title":"J Bone Miner Res"},{"key":"2024020319174135900_jbmr2398-bib-0020","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1002\/jbmr.130","article-title":"Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Sch\u0151nberg disease (chloride channel 7 deficiency osteopetrosis) among the sclerosing bone disorders","volume":"25","author":"Whyte","year":"2010","journal-title":"J Bone Miner Res"},{"key":"2024020319174135900_jbmr2398-bib-0021","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1074\/jbc.M009776200","article-title":"Structure and expression of the murine phosphatidylserine synthase-1 gene","volume":"276","author":"Sturbois-Balcerzak","year":"2001","journal-title":"J Biol Chem"},{"key":"2024020319174135900_jbmr2398-bib-0022","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.bbalip.2012.08.016","article-title":"Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells","volume":"1831","author":"Vance","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"2024020319174135900_jbmr2398-bib-0023","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1042\/BJ20081597","article-title":"Purification and characterization of human phosphatidylserine synthases 1 and 2","volume":"418","author":"Tomohiro","year":"2009","journal-title":"Biochem J"},{"key":"2024020319174135900_jbmr2398-bib-0024","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.biophys.093008.131234","article-title":"The distribution and function of phosphatidylserine in cellular membranes","volume":"39","author":"Leventis","year":"2010","journal-title":"Annu Rev Biophys"},{"key":"2024020319174135900_jbmr2398-bib-0025","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1023\/A:1022412831330","article-title":"Metabolism and functions of phosphatidylserine in mammalian brain","volume":"28","author":"Mozzi","year":"2003","journal-title":"Neurochem Res"},{"key":"2024020319174135900_jbmr2398-bib-0026","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1172\/JCI108390","article-title":"Location of phosphatidylethanolamine and phosphatidylserine in the human platelet plasma membrane","volume":"57","author":"Schick","year":"1976","journal-title":"J Clin Invest"},{"key":"2024020319174135900_jbmr2398-bib-0027","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1126\/science.1411571","article-title":"Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C","volume":"258","author":"Nishizuka","year":"1992","journal-title":"Science"},{"key":"2024020319174135900_jbmr2398-bib-0028","doi-asserted-by":"crossref","first-page":"12888","DOI":"10.1074\/jbc.M800714200","article-title":"Defining the importance of phosphatidylserine synthase-1 (PSS1): unexpected viability of PSS1-deficient mice","volume":"283","author":"Arikketh","year":"2008","journal-title":"J Biol Chem"},{"key":"2024020319174135900_jbmr2398-bib-0029","doi-asserted-by":"crossref","first-page":"47701","DOI":"10.1074\/jbc.M207734200","article-title":"Defining the importance of phosphatidylserine synthase 2 in mice","volume":"277","author":"Bergo","year":"2002","journal-title":"J Biol Chem"},{"key":"2024020319174135900_jbmr2398-bib-0030","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/dnares\/1.1.27","article-title":"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1","volume":"1","author":"Nomura","year":"1994","journal-title":"DNA Res"},{"key":"2024020319174135900_jbmr2398-bib-0031","doi-asserted-by":"crossref","first-page":"S132","DOI":"10.1194\/jlr.R800048-JLR200","article-title":"Physiological consequences of disruption of mammalian phospholipid biosynthetic genes","volume":"50","author":"Vance","year":"2009","journal-title":"J Lipid Res"},{"key":"2024020319174135900_jbmr2398-bib-0032","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/ajmg.a.33909","article-title":"Nosology and classification of genetic skeletal disorders: 2010 revision","volume":"155A","author":"Warman","year":"2011","journal-title":"Am J Med Genet A"},{"key":"2024020319174135900_jbmr2398-bib-0033","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.3390\/molecules14125367","article-title":"Role of phosphatidyl-serine in bone repair and its technological exploitation","volume":"14","author":"Merolli","year":"2009","journal-title":"Molecules"},{"key":"2024020319174135900_jbmr2398-bib-0034","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1016\/S0142-9612(03)00330-2","article-title":"Osteoblast response to phospholipid modified titanium surface","volume":"24","author":"Satsangi","year":"2003","journal-title":"Biomaterials"},{"key":"2024020319174135900_jbmr2398-bib-0035","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.4049\/jimmunol.0803609","article-title":"Phosphatidylserine-containing liposomes inhibit the differentiation of osteoclasts and trabecular bone loss","volume":"184","author":"Wu","year":"2010","journal-title":"J Immunol"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2398","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/30\/4\/606\/56568765\/jbmr2398.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/30\/4\/606\/56568765\/jbmr2398.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:53:13Z","timestamp":1710341593000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/30\/4\/606-614\/7599307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,1]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,11,1]]},"published-print":{"date-parts":[[2015,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.2398","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,4,1]]},"published":{"date-parts":[[2014,11,1]]}}}