{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:09:13Z","timestamp":1791050953237,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,1,26]],"date-time":"2010-01-26T00:00:00Z","timestamp":1264464000000},"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 C"],"published-print":{"date-parts":[[2010,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Here we present a 24\u2010week fetus with Smith\u2013Lemli\u2013Opitz syndrome (SLOS), alobar holoprosencephaly (HPE) and cyclopia (synophthalmia). Following birth, we suspected SLOS in this fetus due to the additional findings of ambiguous genitalia and bilateral 2\u20133 toe syndactyly. The diagnosis of SLOS was confirmed by finding an elevated amniotic fluid 7\u2010dehydrocholesterol level (9,890\u2009ng\/ml; normal range\u2009=\u20093\u20139\u2009ng\/ml), and molecularly by detecting two different mutations in the <jats:italic>DHCR7<\/jats:italic> gene, the gene causing SLOS. The first mutation was an IVS8\u20101G&gt;T change and the second was a deletion of exons 3 and 4; this latter mutation has not been reported previously. The mother carries the deletion, while the father carries the splice\u2010site mutation. Also of note, the father has an abnormally low total plasma cholesterol level (104\u2013109\u2009mg\/dl). This is the most severe case of HPE described in any patient with SLOS. We postulate that the HPE in this case resulted from severe impairment of Sonic Hedgehog signaling secondary to abnormal cholesterol metabolism; however, the unique combination of mutations in the fetus functionally appears to be no different from other homozygous null mutations reported in <jats:italic>DHCR7<\/jats:italic>. Therefore, there must be other yet to be identified factors that contributed to the severity of HPE in SLOS. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.30241","type":"journal-article","created":{"date-parts":[[2010,1,26]],"date-time":"2010-01-26T22:20:09Z","timestamp":1264544409000},"page":"142-145","source":"Crossref","is-referenced-by-count":40,"title":["Cyclopia (synophthalmia) in Smith\u2013Lemli\u2013Opitz syndrome: First reported case and consideration of mechanism"],"prefix":"10.1002","volume":"154C","author":[{"given":"David D.","family":"Weaver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Akin\u2010Samson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard I.","family":"Kelley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Muenke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,1,26]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-003-1110-1"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00350.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5369.1603"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970131)68:3<263::AID-AJMG4>3.0.CO;2-N"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970131)68:3<328::AID-AJMG15>3.0.CO;2-V"},{"key":"e_1_2_5_7_1","unstructured":"HassD MvenkeM.Abnormal sterol metabolism in holoprosencephaly. This issue: manuscipt ID C\u201009\u20100040."},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.5.321"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19961230)66:4<478::AID-AJMG22>3.0.CO;2-Q"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990219)82:5<376::AID-AJMG4>3.0.CO;2-B"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20001113)95:2<174::AID-AJMG16>3.0.CO;2-9"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.27.7.465"},{"key":"e_1_2_5_13_1","first-page":"36A","article-title":"Holoprosencephaly as a manifestation of Smith\u2013Lemli\u2013Opitz syndrome","volume":"55","author":"Muenke M","year":"1994","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010915)103:1<75::AID-AJMG1502>3.0.CO;2-R"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2760(98)00041-1"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/384129a0"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/301982"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8460"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/302760"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.018085"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.c.30241","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.30241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T14:19:29Z","timestamp":1694614769000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.30241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,26]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,2,15]]}},"alternative-id":["10.1002\/ajmg.c.30241"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.30241","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1,26]]}}}