{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:57:26Z","timestamp":1776855446222,"version":"3.51.2"},"reference-count":51,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2019]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder characterized by 3 overlapping phenotypes: salt-wasting (SW), simple virilizing (SV), and non-classic (NC). We aimed at conducting a nationwide genotype description of the CAH pediatric patients and to establish their genotype\u2013phenotype correlation. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; CAH patients were recruited from Portuguese pediatric endocrinology centers and classified as SW, SV, or NC. Genetic analysis was performed by polymerase chain reaction (sequence specific primer, restriction fragment length polymorphism) or direct Sanger sequencing. Genotypes were categorized into 4 groups (0, A, B, and C), according to their predicted enzymatic activity. In each group, the expected phenotype was compared to the observed phenotype to assess the genotype\u2013phenotype correlation. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Our cohort comprises 212 unrelated pediatric CAH patients (29% SW, 11% SV, 60% NC). The most common pathogenic variant was p.(Val282Leu; 41.3% of the 424 alleles analyzed). The p.(Val282Leu) variant, together with c.293-13A\/C&amp;#x3e;G, p.(Ile173Asn), p.(Leu308Thr), p.(Gln319*), and large deletions\/conversions were responsible for 86.4% of the mutated alleles. Patients\u2019 stratification by disease subtype revealed that the most frequent pathogenic variants were c.293-13A\/C&amp;#x3e;G in SW (31.1%), p.(Ile173Asn) in SV (46.9%), and p.(Val282Leu) in NC (69.5%). The most common genotype was homozygosity for p.(Val282Leu; 33.0%). Moreover, we found 2 novel variants: p.(Ile161Thr) and p.(Trp202Arg), in exons 4 and 5, respectively. The global genotype-phenotype correlation was 92.4%. Group B (associated with the SV form) showed the lowest genotype\u2013phenotype correlation (80%). &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Our cohort has one of the largest NC CAH pediatric populations described. We emphasize the high frequency of the p.(Val282Leu) variant and the very high genotype\u2013phenotype correlation observed.<\/jats:p>","DOI":"10.1159\/000497485","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T22:00:27Z","timestamp":1553032827000},"page":"33-45","source":"Crossref","is-referenced-by-count":15,"title":["&lt;b&gt;&lt;i&gt;CYP21A2&lt;\/i&gt;&lt;\/b&gt; Gene Pathogenic Variants: A Multicenter Study on Genotype\u2013Phenotype Correlation from a Portuguese Pediatric Cohort"],"prefix":"10.1159","volume":"91","author":[{"given":"Rita","family":"Santos-Silva","sequence":"first","affiliation":[]},{"given":"Rita","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Lurdes","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Marcelo","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Filipa","family":"Espada","sequence":"additional","affiliation":[]},{"given":"Lurdes","family":"Sampaio","sequence":"additional","affiliation":[]},{"given":"Carla","family":"Brand\u00e3o","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Antunes","sequence":"additional","affiliation":[]},{"given":"Graciete","family":"Bragan\u00e7a","sequence":"additional","affiliation":[]},{"given":"Raquel","family":"Coelho","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Bernardo","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Morais","sequence":"additional","affiliation":[]},{"given":"Ana\u00a0Lu\u00edsa","family":"Leite","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Ribeiro","sequence":"additional","affiliation":[]},{"given":"Berta","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Grangeia","sequence":"additional","affiliation":[]},{"given":"Renata","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Maria\u00a0Jo\u00e3o","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Vicente","family":"Rey","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Rosmaninho-Salgado","sequence":"additional","affiliation":[]},{"given":"Bernardo","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Ana\u00a0Margarida","family":"Garcia","sequence":"additional","affiliation":[]},{"given":"Andreia","family":"Meireles","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Ana\u00a0","family":"Sequeira","sequence":"additional","affiliation":[]},{"given":"Alice","family":"Mirante","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Borges","sequence":"additional","affiliation":[]},{"name":"on\u00a0behalf\u00a0of\u00a0the\u00a0Portuguese\u00a0Society\u00a0of\u00a0Pediatric\u00a0Endocrinology\u00a0and\u00a0Diabetology","sequence":"additional","affiliation":[]}],"member":"127","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23351"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.46"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.06.015"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2016.01.007"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1728"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.2165\/00129785-200101020-00003"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2011.04123.x"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1177\/0300060516685204"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.3.6441"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.03.035"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300057110"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.10.3293"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.11.015"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1237363"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/S0932-8610(12)80154-X"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2006.02465.x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1323805"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1099"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115897"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0319"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3343"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1159\/000321223"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01865"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.07.027"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.4008\/jcrpe.v1i3.49"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.1.7131"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2000.01048.x"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb02851.x"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1998.00402.x"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3543"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2002.620213.x"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-015-0366-8"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021681"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0379"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-27302004000500016"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1159\/000022866"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.01944"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2011.0099"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1287789"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2015.07.022"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.07.009"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.3109\/07435809509030452"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2631"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380050205"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050394"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1999)13:6<482::AID-HUMU8>3.0.CO;2-0"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1998.tb00968.x"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050672"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.6.8522"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/497485","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/497485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:18:52Z","timestamp":1745425132000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000497485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,5,16]]},"published-print":{"date-parts":[[2019,5,20]]}},"URL":"https:\/\/doi.org\/10.1159\/000497485","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019]]}}}