{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:04:37Z","timestamp":1766869477156},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:label \/><jats:p>We report on a family in which four males over three generations are affected with X\u2010linked recessive developmental delay, learning difficulties, severe behavioral difficulties and mild dysmorphic features. Plasma sterol analysis in three of the four affected males demonstrated increased concentrations of 8\u2010dehydrocholesterol (8\u2010DHC) and cholest\u20108(9)\u2010enol. All four affected males had a novel hemizygous missense mutation, p.W47R (c.139T&gt;C), in <jats:italic>EBP<\/jats:italic>. Functional studies showed raised levels of cholest\u20108(9)\u2010enol in patient's cultured fibroblast cells, which were suppressed when the cells were incubated with simvastatin. <jats:italic>EBP<\/jats:italic> encodes 3\u03b2\u2010hydroxysteroid\u2010delta8, delta7\u2010isomerase, a key enzyme involved in the cholesterol biosynthesis pathway. Mutations in <jats:italic>EBP<\/jats:italic> have previously been associated with Conradi\u2013Hunermann\u2013Happle syndrome (CHH), an X\u2010linked dominant disorder characterized by skeletal dysplasia, skin, and ocular abnormalities, which is usually lethal in males. Four previous reports describe X\u2010linked recessive multiple anomaly syndromes associated with non\u2010mosaic <jats:italic>EBP<\/jats:italic> mutations in males, two at the same amino acid position, p.W47C. This phenotype has previously been described as \u201cMEND\u201d syndrome (male <jats:italic>EBP<\/jats:italic> disorder with neurological defects). The family reported herein represent either a novel phenotype, or an expansion of the MEND phenotype, characterized by extreme behavioral difficulties and a scarcity of structural anomalies. Simvastatin therapy is being evaluated in two males from this family. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36368","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T23:39:04Z","timestamp":1390520344000},"page":"907-914","source":"Crossref","is-referenced-by-count":12,"title":["An unusual phenotype of X\u2010linked developmental delay and extreme behavioral difficulties associated with a mutation in the EBP gene"],"prefix":"10.1002","volume":"164","author":[{"given":"Verity L.","family":"Hartill","sequence":"first","affiliation":[{"name":"Yorkshire Regional Genetics Service Chapel Allerton Hospital Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Tysoe","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Royal Devon and Exeter NHS Foundation Trust Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Sheffield Children's Hospital Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus","family":"Dobbie","sequence":"additional","affiliation":[{"name":"Yorkshire Regional Genetics Service Chapel Allerton Hospital Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saikat","family":"Santra","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine Birmingham Children's Hospital Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Walter","sequence":"additional","affiliation":[{"name":"Willink Biochemical Genetics Unit Manchester Academic Health Science Centre, University of Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Caswell","sequence":"additional","affiliation":[{"name":"Institute for Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Koster","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Metabolic Diseases, Academic Medical Centre University of Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Waterham","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Metabolic Diseases, Academic Medical Centre University of Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Hobson","sequence":"additional","affiliation":[{"name":"Yorkshire Regional Genetics Service Chapel Allerton Hospital Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10808.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10852"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/10357"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31819ea4eb"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1001\/archderm.1985.01660080118029","article-title":"Acute skin manifestations of Conradi\u2013Hunermann Syndrome in a male adult","volume":"121","author":"Crovato F","year":"1985","journal-title":"Arch Dermatol"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000248418"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/10350"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31342"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00500.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970131)68:3<305::AID-AJMG11>3.0.CO;2-X"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNN.0b013e31828bf6d5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33674"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0537-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00273442"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570327"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20324"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33988"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01761.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348948709600517"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970131)68:3<311::AID-AJMG12>3.0.CO;2-W"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)33442-8"},{"key":"e_1_2_7_23_1","first-page":"95","article-title":"The male with Conradi\u2013Hunermann\u2013Happle syndrome (CPX2): A distinct phenotype","volume":"24","author":"Kelley RI","year":"2005","journal-title":"Proc Greenwood Genet Centre"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10849"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970131)68:3<315::AID-AJMG13>3.0.CO;2-W"},{"key":"e_1_2_7_26_1","first-page":"117","article-title":"Chrondrodysplasia punctata (the Conradi\u2013Hunermann syndrome). A clinical case and review of the literature","volume":"45","author":"Omobono E","year":"1993","journal-title":"Minerva Pediatr"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34089"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22434"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10722"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570326"},{"key":"e_1_2_7_31_1","unstructured":"TanC HaverfieldE DempseyM KratzL DescartesM PowellB.2010. X\u2010linked dominant chondrodysplasia punctata andEBPmutations in males. American College of Medical Genetics Annual Clinical Genetics Meeting Poster Presentation."},{"key":"e_1_2_7_32_1","first-page":"221","article-title":"X\u2010chromosome dominant chondrodysplaisa punctata (Happle) in a boy","volume":"43","author":"Tronnier M","year":"1992","journal-title":"Hautarzt"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/301936"}],"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.36368","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36368","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T02:13:22Z","timestamp":1696558402000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,23]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1002\/ajmg.a.36368"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36368","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,23]]}}}