{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:25:18Z","timestamp":1782707118216,"version":"3.54.5"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1248,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RL1HL092550"],"award-info":[{"award-number":["RL1HL092550"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["PO1 HL20948"],"award-info":[{"award-number":["PO1 HL20948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>The most common inborn error of bile acid metabolism is 3\u03b2-hydroxy-\u0394<jats:sup>5<\/jats:sup>-C<jats:sub>27<\/jats:sub>-steroid oxidoreductase (3\u03b2-HSD) deficiency, a disorder that usually presents in early childhood with hepatic dysfunction. Timely diagnosis of this disorder is crucial because it can be effectively treated with primary bile acid replacement. Here we describe a 24-year-old woman from Iran with cirrhosis of unknown etiology. Her sister and a first cousin died of cirrhosis (ages 19 and 6 years) and another 32-year-old first cousin had a self-limited liver disorder in childhood that resolved at age 9 years. The family history suggested that the affected family members were homozygous for a mutant allele inherited identical-by-descent. A genome-wide analysis of 2.4 million single nucleotide polymorphisms was performed to identify regions of homozygosity that were present in the proband and the 32-year-old first cousin, but not in a healthy relative. One of these regions contained the gene encoding 3\u03b2-HSD (<jats:italic toggle=\"yes\">HSD3B7<\/jats:italic>). Sequence analysis of <jats:italic toggle=\"yes\">HSD3B7<\/jats:italic> revealed that the proband and her 32-year-old cousin were homozygous for a frameshift mutation (c.45_46del AG, p.T15Tfsx27) in exon 1. The diagnosis of 3\u03b2-HSD deficiency was confirmed by documenting high levels of 3\u03b2-hydroxy-\u0394<jats:sup>5<\/jats:sup> bile acids in the serum of the proband and the 32-year-old first cousin using mass spectrometry. To our knowledge, the 32-year-old relative in this family represents the oldest asymptomatic patient with this disorder. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: This study highlights the clinical utility of homozygosity mapping in diagnosing autosomal recessive metabolic disorders. This family illustrates the wide variation in expressivity that occurs in 3\u03b2-HSD deficiency and underscores the need to consider a bile acid synthetic defect as a possible cause of liver disease in adults. (Hepatology 2012)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24781","type":"journal-article","created":{"date-parts":[[2011,11,17]],"date-time":"2011-11-17T07:53:03Z","timestamp":1321516383000},"page":"1139-1145","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":36,"title":["Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology"],"prefix":"10.1097","volume":"55","author":[{"given":"Vered","family":"Molho-Pessach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth D.R.","family":"Setchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H.","family":"Hobbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"issue":"Suppl","key":"R1-17-20241201","first-page":"S120S125","article-title":"Fifty years of advances in bile acid synthesis and metabolism.","volume":"50","author":"Russell","year":"2009","journal-title":"J Lipid Res"},{"key":"R3-17-20241201","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1210\/jc.2002-021580","article-title":"Molecular genetics of 3betahydroxyDelta5C27steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.","volume":"88","author":"Cheng","year":"2003","journal-title":"J Clin Endocrinol 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adulthood.","volume":"120","author":"Jacquemin","year":"2001","journal-title":"Gastroenterology"},{"key":"R11-17-20241201","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1046\/j.1442-200x.2000.01292.x","article-title":"3betahydroxydelta5C27steroid dehydrogenaseisomerase deficiency in a 23yearold woman.","volume":"42","author":"Kobayashi","year":"2000","journal-title":"Pediatr Int"},{"key":"R12-17-20241201","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1203\/PDR.0b013e3181eb0188","article-title":"Molecular genetic and bile acid profiles in two Japanese patients with 3betahydroxyDELTA5C27steroid dehydrogenaseisomerase deficiency.","volume":"68","author":"Mizuochi","year":"2010","journal-title":"Pediatr Res"},{"key":"R13-17-20241201","doi-asserted-by":"crossref","first-page":"e192e195","DOI":"10.1111\/j.1442-200X.2010.03131.x","article-title":"3betahydroxyDeltaCsteroid dehydrogenaseisomerase deficiency in a patient who underwent oral bile acid therapy for 10 years 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