{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T11:49:33Z","timestamp":1708516173219},"reference-count":34,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,11,1]]},"abstract":"<jats:p>Premature stop codons of the human androgen receptor (AR) gene are usually associated with a complete androgen insensitivity syndrome. We, however, identified an adult patient with a 46,XY karyotype carrying a premature stop codon in exon 1 of the AR gene presenting with signs of partial virilization: pubic hair Tanner stage 4 and clitoral enlargement. No other family members were affected. A point mutation at codon position 172 of the AR gene was detected that replaced the original TTA (Leu) with a premature stop codon TGA (opal). Careful examination of the sequencing gel, however, also identified a wild-type allele, indicating a mosaicism. In addition, elimination of the unique AflII recognition site induced by the mutation was incomplete, thus confirming the coexistence of mutant and wild-type AR alleles in the patient. Normal R1881 binding and a normal 110\/112-kDa AR doublet in Western immunoblots consolidated the molecular genetic data by demonstrating the expression of the wild-type AR in the patient\u2019s genital skin fibroblasts. Transfection analysis revealed that only relatively high plasmid concentrations carrying the mutated AR complementary DNA lead to expression of a shortened AR due to downstream reinitiation at methionine 189. Thus, reinitiation does not play a role in the presentation of the phenotype; rather, the partial virilization is caused by the expression of the wild-type AR due to a somatic mosaic. We conclude that somatic mosaicism of the AR gene can represent a substantial factor for the individual phenotype by shifting it to a higher degree of virilization than expected from the genotype of the mutant allele alone.<\/jats:p>","DOI":"10.1210\/jcem.82.11.4375","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:10Z","timestamp":1389200470000},"page":"3584-3589","source":"Crossref","is-referenced-by-count":2,"title":["Mosaicism due to a Somatic Mutation of the Androgen Receptor Gene Determines Phenotype in Androgen Insensitivity Syndrome1"],"prefix":"10.1210","volume":"82","author":[{"given":"Paul-Martin","family":"Holterhus","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical University of Lu\u0308beck (P.M.H., O.H., K.K., G.H.G.S.), Lu\u0308beck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hennie T.","family":"Bru\u0308ggenwirth","sequence":"additional","affiliation":[{"name":"the Department of Endocrinology and Reproduction, Erasmus University (H.T.B., A.O.B.), Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Hiort","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical University of Lu\u0308beck (P.M.H., O.H., K.K., G.H.G.S.), Lu\u0308beck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Kleinkauf-Houcken","sequence":"additional","affiliation":[{"name":"the Department of Gynecologic Endocrinology and Reproductive Medicine, University Hospital (A.K.H.), Hamburg-Eppendorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Kruse","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical University of Lu\u0308beck (P.M.H., O.H., K.K., G.H.G.S.), Lu\u0308beck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gernot H. G.","family":"Sinnecker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical University of Lu\u0308beck (P.M.H., O.H., K.K., G.H.G.S.), Lu\u0308beck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert O.","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"the Department of Endocrinology and Reproduction, Erasmus University (H.T.B., A.O.B.), Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071620554546000_R1","first-page":"271","article-title":"Androgen receptor defects: historical, clinical, and molecular perspectives.","volume":"16","author":"Quigley","year":"1995","journal-title":"Endocr Rev"},{"key":"2020071620554546000_R2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0960-0760(93)90178-Y","article-title":"Mutations of androgen receptor gene in androgen insensitivity syndromes. 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