{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:30:41Z","timestamp":1791300641503,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T00:00:00Z","timestamp":1543190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Polyamines serve a number of vital functions in humans, including regulation of cellular proliferation, intracellular signaling, and modulation of ion channels. Ornithine decarboxylase 1 (ODC1) is the rate\u2010limiting enzyme in endogenous polyamine synthesis. In this report, we present four patients with a distinct neurometabolic disorder associated with de novo heterozygous, gain\u2010of\u2010function variants in the <jats:italic>ODC1<\/jats:italic> gene. This disorder presents with global developmental delay, ectodermal abnormalities including alopecia, absolute or relative macrocephaly, and characteristic facial dysmorphisms. Neuroimaging variably demonstrates white matter abnormalities, prominent Virchow\u2013Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. Plasma clinical metabolomics analysis demonstrates elevation of <jats:italic>N<\/jats:italic>\u2010acetylputrescine, the acetylated form of putrescine, with otherwise normal polyamine levels. Therapies aimed at reducing putrescine levels, including ODC1 inhibitors, dietary interventions, and antibiotics to reduce polyamine production by gastrointestinal flora could be considered as disease\u2010modifying therapies. As the <jats:italic>ODC1<\/jats:italic> gene has been implicated in neoplasia, cancer surveillance may be important in this disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.60677","type":"journal-article","created":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T15:01:47Z","timestamp":1543244507000},"page":"2554-2560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Gain\u2010of\u2010function variants in the <i>ODC1<\/i> gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-6688","authenticated-orcid":false,"given":"Lance H.","family":"Rodan","sequence":"first","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital, Harvard Medical School  Boston Massachusetts"},{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwame","family":"Anyane\u2010Yeboa","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Pediatrics Columbia University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chong","sequence":"additional","affiliation":[{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology Mount Sinai Hospital, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien S.","family":"Klein Wassink\u2010Ruiter","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Pediatrics Columbia University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey","family":"Smith","sequence":"additional","affiliation":[{"name":"Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology Boston Children's Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev V.","family":"Kothare","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwell Health, Zucker School of Medicine at Hofstra\/Northwell  New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrah","family":"Rajabi","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Blaser","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology The Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ni","sequence":"additional","affiliation":[{"name":"Children's Medical Center Research Institute University of Texas Southwestern Medical Center  Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph J.","family":"DeBerardinis","sequence":"additional","affiliation":[{"name":"Children's Medical Center Research Institute University of Texas Southwestern Medical Center  Dallas Texas"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center  Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annapurna","family":"Poduri","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts"},{"name":"Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology Boston Children's Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard T.","family":"Berry","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00060"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/bse0460009"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.02.008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40523"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00806001"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aninu.2016.12.002"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2910505"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2011.09.007"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1880263"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2004.11.001"},{"issue":"4","key":"e_1_2_6_12_1","article-title":"Regulation of polyamine metabolism by Curcumin for cancer prevention and therapy","volume":"5","author":"Murray\u2010Stewart T.","year":"2017","journal-title":"Medical Science"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2013.3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.15"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12340155"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01957284"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(90)90199-V"},{"issue":"141","key":"e_1_2_6_18_1","first-page":"1","article-title":"GABA as a rising gliotransmitter","volume":"8","author":"Yoon B. E.","year":"2014","journal-title":"Front Neural Circuits"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.60677","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.60677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:47:33Z","timestamp":1694684853000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.60677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,26]]},"references-count":17,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/ajmg.a.60677"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.60677","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,26]]},"assertion":[{"value":"2018-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}