{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:45:40Z","timestamp":1787240740217,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,17]],"date-time":"2013-08-17T00:00:00Z","timestamp":1376697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Summary<\/jats:title>\n \n Objective<\/jats:title>\n \n The steroidogenic acute regulatory protein (\n S<\/jats:styled-content>\n t\n AR<\/jats:styled-content>\n ) transports cholesterol to the mitochondria for steroidogenesis. Loss of\n S<\/jats:styled-content>\n t\n AR<\/jats:styled-content>\n function causes lipoid congenital adrenal hyperplasia (\n LCAH<\/jats:styled-content>\n ) which is characterized by impaired synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,\n XY<\/jats:styled-content>\n disorder of sex development (\n DSD<\/jats:styled-content>\n ) and failure of pubertal development. Partial loss of\n S<\/jats:styled-content>\n t\n AR<\/jats:styled-content>\n activity may cause adrenal insufficiency only.\n <\/jats:p>\n <\/jats:sec>\n \n Patient<\/jats:title>\n \n A newborn girl was admitted for mild dehydration, hyponatremia, hyperkalemia and hypoglycaemia and had normal external female genitalia without hyperpigmentation. Plasma cortisol, 17\n OH<\/jats:styled-content>\n \u2010progesterone,\n DHEA<\/jats:styled-content>\n \u2010\n S<\/jats:styled-content>\n , androstendione and aldosterone were low, while\n ACTH<\/jats:styled-content>\n and plasma renin activity were elevated, consistent with the diagnosis of primary adrenal insufficiency. Imaging showed normal adrenals, and cytogenetics revealed a 46,\n XX<\/jats:styled-content>\n karyotype. She was treated with fluids, hydrocortisone and fludrocortisone.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Methods and Results<\/jats:title>\n \n Genetic studies revealed a novel homozygous\n \n STAR<\/jats:styled-content>\n <\/jats:italic>\n mutation in the 3\u2032 acceptor splice site of intron 4, c.466\u20101G>A (IVS4\u20101G>A). To test whether this mutation would affect splicing, we performed a minigene experiment with a plasmid construct containing wild\u2010type or mutant\n S<\/jats:styled-content>\n t\n AR<\/jats:styled-content>\n g\n DNA<\/jats:styled-content>\n of exons\u2013introns 4\u20136 in\n COS<\/jats:styled-content>\n \u20101 cells. The splicing was assessed on total\n RNA<\/jats:styled-content>\n using\n RT\u2010PCR<\/jats:styled-content>\n for\n \n STAR<\/jats:styled-content>\n <\/jats:italic>\n c\n DNA<\/jats:styled-content>\n s. The mutant\n \n STAR<\/jats:styled-content>\n <\/jats:italic>\n minigene skipped exon 5 completely and changed the reading frame. Thus, it is predicted to produce an aberrant and shorter protein (p.V156GfsX19). Computational analysis revealed that this mutant protein lacks wild\u2010type exons 5\u20137 which are essential for StAR\u2010cholesterol interaction.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n \n STAR<\/jats:styled-content>\n <\/jats:italic>\n c.466\u20101A skips exon 5 and causes a dramatic change in the\n C<\/jats:styled-content>\n \u2010terminal sequence of the protein, which is essential for\n S<\/jats:styled-content>\n t\n AR<\/jats:styled-content>\n \u2013cholesterol interaction. This splicing mutation is a loss\u2010of\u2010function mutation explaining the severe phenotype of our patient. Thus far, all reported splicing mutations of\n \n STAR<\/jats:styled-content>\n <\/jats:italic>\n cause a severe impairment of protein function and phenotype.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cen.12293","type":"journal-article","created":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T10:23:04Z","timestamp":1373970184000},"page":"191-199","source":"Crossref","is-referenced-by-count":19,"title":["\n STAR<\/scp>\n <\/i>\n splicing mutations cause the severe phenotype of lipoid congenital adrenal hyperplasia: insights from a novel splice mutation and review of reported cases"],"prefix":"10.1111","volume":"80","author":[{"given":"N\u00faria","family":"Camats","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Department of Pediatrics and Department of Clinical Research University Children's Hospital Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit V.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Department of Pediatrics and Department of Clinical Research University Children's Hospital Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Fern\u00e1ndez\u2010Cancio","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Research Unit Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona Center for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Service Hospital Cl\u00ednico Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Ortega","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Service Hospital Cl\u00ednico Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Udhane","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Department of Pediatrics and Department of Clinical Research University Children's Hospital Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Andaluz","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Research Unit Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona Center for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Aud\u00ed","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Research Unit Vall d'Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona Center for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa E.","family":"Fl\u00fcck","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Department of Pediatrics and Department of Clinical Research University Children's Hospital Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7892608"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199612193352503"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0874"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0467"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020178"},{"key":"e_1_2_8_7_1","first-page":"2337","article-title":"A novel splicing junction mutation in the gene for the steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia","volume":"82","author":"Okuyama E.","year":"1997","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1565"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000342504"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2865"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.02082"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.04.052"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.10.3636"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030345"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3202"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.4.571"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1420274"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.5.1511"},{"key":"e_1_2_8_19_1","first-page":"585","article-title":"[Molecular genetic analysis of congenital lipoid adrenal hyperplasia]. Zhonghua er ke za zhi","volume":"42","author":"Qiu W.J.","year":"2004","journal-title":"Chinese Journal of Pediatrics"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0434"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1306"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1176"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1323"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.12.2299"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20080111"},{"key":"e_1_2_8_26_1","first-page":"3983","article-title":"A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia","volume":"84","author":"Katsumata N.","year":"1999","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0437"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119284"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:4<331::AID-HUMU12>3.0.CO;2-3"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1210\/jcem.84.5.5694","article-title":"Gonadal histology with testicular carcinoma in situ in a 15\u2010year\u2010old 46, XY female patient with a premature termination in the steroidogenic acute regulatory protein causing congenital lipoid adrenal hyperplasia","volume":"84","author":"Korsch E.","year":"1999","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1620-5"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0597"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.12.016"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem.2010.196"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019521"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/75192"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13731"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12293","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T22:33:48Z","timestamp":1696286028000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,17]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1111\/cen.12293"],"URL":"https:\/\/doi.org\/10.1111\/cen.12293","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,17]]}}}