{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:58:26Z","timestamp":1778943506843,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,4,25]],"date-time":"2002-04-25T00:00:00Z","timestamp":1019692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[2002,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antley\u2010Bixler syndrome (ABS) is a rare multiple anomaly syndrome comprising radiohumeral synostosis, bowed femora, fractures of the long bones, premature fusion of the calvarial sutures, severe midface hypoplasia, proptosis, choanal atresia, and, in some, ambiguous genitalia. Of fewer than 40 patients described to date, most have been sporadic, although reports of parental consanguinity and affected sibs of both sexes suggests autosomal recessive inheritance in some families. Known genetic causes among sporadic cases of ABS or ABS\u2010like syndromes are missense mutations in the IgII and IgIII regions of<jats:italic>FGFR2<\/jats:italic>, although the assignment of the diagnosis of ABS to such children has been disputed. A third cause of an ABS\u2010like phenotype is early in utero exposure to fluconazole, an inhibitor of lanosterol 14\u2010alpha\u2010demethylase. The fourth proposed cause of ABS is digenic inheritance combining heterozygosity or homozygosity for steroid 21\u2010hydroxylase deficiency with effects from a second gene at an unknown locus. Because fluconazole is a strong inhibitor of lanosterol 14\u2010alpha\u2010demethylase (CYP51), we evaluated sterol metabolism in lymphoblast cell lines from an ABS patient without a known<jats:italic>FGFR2<\/jats:italic>mutation and from a patient with an<jats:italic>FGFR2<\/jats:italic>mutation and ABS\u2010like manifestations. When grown in the absence of cholesterol to stimulate cholesterol biosynthesis, the cells from the ABS patient with ambiguous genitalia but without an<jats:italic>FGFR2<\/jats:italic>mutation accumulated markedly increased levels of lanosterol and dihydrolanosterol. Although the abnormal sterol profile suggested a deficiency of lanosterol 14\u2010alpha\u2010demethylase, mutational analysis of its gene,<jats:italic>CYP51<\/jats:italic>, disclosed no obvious pathogenic mutation in any of its 10 exons or exon\u2010intron boundaries. Sterol metabolism in lymphoblasts from the phenotypically unaffected mother was normal. Our results suggest that ABS can occur in a patient with an intrinsic defect of cholesterol biosynthesis at the level of lanosterol 14\u2010alpha\u2010demethylase, although the genetic nature of the deficiency remains to be determined. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.10510","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:27:22Z","timestamp":1033907242000},"page":"95-102","source":"Crossref","is-referenced-by-count":77,"title":["Abnormal sterol metabolism in a patient with Antley\u2010Bixler syndrome and ambiguous genitalia"],"prefix":"10.1002","volume":"110","author":[{"given":"Richard I.","family":"Kelley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa E.","family":"Kratz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rivka 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