{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T16:18:37Z","timestamp":1776010717965,"version":"3.50.1"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"04","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Key Research and Development Project by Department of Science\n                        and Technology in Sichuan Province","award":["2022YFS0042"],"award-info":[{"award-number":["2022YFS0042"]}]},{"name":"National Natural Science Foundation for Young Scientists of\n                        China","award":["82001560"],"award-info":[{"award-number":["82001560"]}]},{"DOI":"10.13039\/501100019538","name":"Science Foundation for Young Scientists of Sichuan\n                        Province","doi-asserted-by":"crossref","award":["2023NSFSC1608"],"award-info":[{"award-number":["2023NSFSC1608"]}],"id":[{"id":"10.13039\/501100019538","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Z Geburtshilfe Neonatol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intrahepatic cholestasis of pregnancy (ICP) is a\n                        pregnancy-specific liver disease characterized by pruritus and elevated total\n                        bile acid (TBA) levels. The most serious impact of ICP is sudden unexplained\n                        intrauterine fetal death, especially when an associated TBA \u2265 100 \u00b5mol\/L is\n                        confirmed.<\/jats:p><jats:p>We report a case of a 27-year-old female patient with early-onset\n                        severe refractory ICP. Whole-exome sequencing and mutation analyses were\n                        performed to obtain genetic data on the patient and her mother. Sanger\n                        sequencing was performed to screen the mutation site. Computer-based algorithms\n                        were applied to predict the pathogenesis of the identified mutation.\n                        Subsequently, we conducted a literature review to characterize the pathological\n                        features and perinatal management of severe refractory ICP, especially ICP with\n                        genetic susceptibility.<\/jats:p><jats:p>A heterozygous mutation in the ABCD3 gene: c.130C &gt;\n                        T\/p.Pro44Ser was detected in this patient. Through the analysis of pathogenicity\n                        prediction software, the mutations were disease-causing. This is the first\n                        report to identify the novel p.Pro44Ser mutations of ABCD3 gene in ICP\n                        patients.<\/jats:p><jats:p>Our report provides new insights into the genetic\n                        architecture of ICP involving ABCD3 variants. Early-onset severe\n                        refractory ICP is rare and mutations in bile acid metabolism genes might\n                        accentuate the phenotype. Emphasized perinatal management and screening for\n                        potential pathogenicity sites of variants that drive specific recognition of ICP\n                        is necessary.<\/jats:p>","DOI":"10.1055\/a-2468-5250","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T18:52:58Z","timestamp":1736967178000},"page":"288-293","source":"Crossref","is-referenced-by-count":2,"title":["Whole-exome sequencing identifies novel mutation in intrahepatic\n                    cholestasis of pregnancy: A case report and literature review"],"prefix":"10.1055","volume":"229","author":[{"given":"Tingting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan\n                    University West China Second University Hospital, Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of\n                    Women and Children, Sichuan University West China Second University Hospital,\n                    Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-1251","authenticated-orcid":false,"given":"Xiaodong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan\n                    University West China Second University Hospital, Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of\n                    Women and Children, Sichuan University West China Second University Hospital,\n                    Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xixi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan\n                    University West China Second University Hospital, Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of\n                    Women and Children, Sichuan University West China Second University Hospital,\n                    Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan\n                    University West China Second University Hospital, Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of\n                    Women and Children, Sichuan University West China Second University Hospital,\n                    Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchi","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan\n                    University West China Second University Hospital, Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of\n                    Women and Children, Sichuan University West China Second University Hospital,\n                    Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sichuan\n                    University West China Second University Hospital, Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of\n                    Women and Children, Sichuan University West China Second University Hospital,\n                    Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1111\/1471-0528.17206","article-title":"Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022","volume":"129","author":"J Girling","year":"2022","journal-title":"BJOG"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","article-title":"Association of adverse perinatal outcomes of intrahepatic cholestasis of\n                    pregnancy with biochemical markers: results of aggregate and individual patient\n                    data meta-analyses","volume":"393","author":"C Ovadia","year":"2019","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/ajo.13719","article-title":"Intrahepatic cholestasis of pregnancy \u2013 Diagnosis and management: A consensus\n                    statement of the Society of Obstetric Medicine of Australia and New Zealand\n                    (SOMANZ): Executive summary","volume":"63","author":"W M Hague","year":"2023","journal-title":"Aust N Z J Obstet Gynaecol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1038\/s41467-022-29931-z","article-title":"GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple\n                    hepatic genes and regulatory elements","volume":"13","author":"P H Dixon","year":"2022","journal-title":"Nat Comm"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1053\/j.gastro.2003.06.005","article-title":"Enterohepatic bile salt transporters in normal physiology and liver disease","volume":"126","author":"G A Kullak-Ublick","year":"2004","journal-title":"Gastroenterology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/j.2040-4603.2013.tb00519.x","article-title":"Bile formation and secretion","volume":"3","author":"J L Boyer","year":"2013","journal-title":"Compr Physiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/hmg\/ddu448","article-title":"A novel bile acid biosynthesis defect due to a deficiency of peroxisomal\n                    ABCD3","volume":"24","author":"S Ferdinandusse","year":"2015","journal-title":"Hum Mol Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.clinre.2012.06.006","article-title":"The bile salt export pump (BSEP) in health and disease","volume":"36","author":"R Kubitz","year":"2012","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jhep.2009.11.012","article-title":"Liver disease associated with canalicular transport defects: current and future\n                    therapies","volume":"52","author":"J M Stapelbroek","year":"2010","journal-title":"J Hepatol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12884-020-03481-y","article-title":"A multi-centre, open label, randomised, parallel-group, superiority Trial to\n                    compare the efficacy of URsodeoxycholic acid with RIFampicin in the management\n                    of women with severe early onset Intrahepatic Cholestasis of pregnancy: the\n                    TURRIFIC randomised trial","volume":"21","author":"W M Hague","year":"2021","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1111\/j.1572-0241.2006.00695.x","article-title":"Identification of a novel 974C-->G nonsense mutation of the MRP2\/ABCC2 gene\n                    in a patient with Dubin-Johnson syndrome and analysis of the effects of\n                    rifampicin and ursodeoxycholic acid on serum bilirubin and bile acids","volume":"101","author":"C Corpechot","year":"2006","journal-title":"Am J Gastroenterol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41574-019-0266-7","article-title":"Bile acids in glucose metabolism and insulin signalling \u2013 mechanisms and\n                    research needs","volume":"15","author":"T R Ahmad","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1097\/AOG.0000000000001748","article-title":"Managing recurring obstetric cholestasis with metformin","volume":"128","author":"A Elfituri","year":"2016","journal-title":"Obstet Gynecol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"568","DOI":"10.14309\/ajg.0000000000001132","article-title":"Burden of future liver abnormalities in patients with intrahepatic cholestasis\n                    of pregnancy","volume":"116","author":"E Monrose","year":"2021","journal-title":"Am J Gastroenterol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.jhep.2015.03.010","article-title":"Intrahepatic cholestasis of pregnancy and cancer, immune-mediated and\n                    cardiovascular diseases: A population-based cohort study","volume":"63","author":"E A Wikstr\u00f6m Shemer","year":"2015","journal-title":"J Hepatol"}],"container-title":["Zeitschrift f\u00fcr Geburtshilfe und Neonatologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2468-5250.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T22:40:59Z","timestamp":1754692859000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2468-5250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":15,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2025,8,8]]},"published-print":{"date-parts":[[2025,8]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2468-5250","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0948-2393","1439-1651"],"issn-type":[{"value":"0948-2393","type":"print"},{"value":"1439-1651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]}}}