{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:08:43Z","timestamp":1792663723827,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T00:00:00Z","timestamp":1274918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Couples at risk of severe congenital adrenal hyperplasia (CAH) may be offered prenatal treatment or preimplantation diagnosis. However, proper genetic counselling requires the accurate identification of apparently \u2018mild alleles\u2019 in partners of CAH\u2010carriers\/patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CYP21A2 gene analyses were performed in 255 patients with severe 21\u2010hydroxylase deficiency (21\u2010OHD), 94 with mild 21\u2010OHD, 752 parental samples, 233 clinically unaffected partners and 253 historic DNA samples. GENSCAN and ClustalX2.0 software were used for <jats:italic>in silico<\/jats:italic> analyses, and <jats:italic>Epidat 3.1<\/jats:italic> software for statistical calculations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010seven partners were carriers of p.Val282Leu (alias p.Val281Leu, allele frequency 11.7%, 7.4\u201316.1). \u2018Val282Leu alleles\u2019 were detected in 30 patients with salt\u2010wasting (SW) disease, 21 with other pseudogene\u2010derived and rare coding <jats:italic>cis<\/jats:italic> severe mutations, and 9 without. These CYP21A2 genes were compared to those of 94 fully characterized patients with mild deficiency carrying p.Val282Leu in compound heterozygosity with a severe allele. A rare intronic variant, c.292+5G&gt;A, was detected in the nine \u2018severe Val282Leu alleles\u2019 and that was not seen in mild p.Val282Leu alleles, in other deficient alleles or in normal chromosomes. The <jats:italic>in silico<\/jats:italic> documented effect on splicing and the clinical association (p &lt; 0.0001) confirmed p.Val282Leu; c.292+5G&gt;A as a severe allele.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As only severe alleles require clinical intervention, CAH\u2010carrier detection of p.Val282Leu should be followed by the analysis of c.292+5G&gt;A. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.2537","type":"journal-article","created":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T10:20:11Z","timestamp":1274955611000},"page":"758-763","source":"Crossref","is-referenced-by-count":13,"title":["Carrier detection and prenatal diagnosis of congenital adrenal hyperplasia must identify \u2018apparently mild\u2019 CYP21A2 alleles which associate neonatal salt\u2010wasting disease"],"prefix":"10.1002","volume":"30","author":[{"given":"Bego\u00f1a","family":"Ezquieta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Santom\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Barrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Barrionuevo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"L\u00f3pez\u2010Siguero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildefonso","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Mu\u00f1oz\u2010Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0043-7"},{"key":"e_1_2_5_3_1","first-page":"127","volume-title":"Computational Methods in Molecular Biology","author":"Burge CB","year":"1998"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.0951"},{"key":"e_1_2_5_5_1","first-page":"188","article-title":"Consensus statement on 21\u2010hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society","volume":"5","author":"Clayton PE","year":"2002","journal-title":"Horm Res"},{"key":"e_1_2_5_6_1","unstructured":"CooperDN BallEV StensonPD et al.2008.The Human Gene Mutation Database (HGMD). 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