{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:44:01Z","timestamp":1790793841518,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2007,1,2]],"date-time":"2007-01-02T00:00:00Z","timestamp":1167696000000},"content-version":"vor","delay-in-days":1615,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Paediatrica"],"published-print":{"date-parts":[[2002,8]]},"abstract":"<jats:p> <jats:italic>Aim<\/jats:italic>: To investigate the association between levels of 17\u2010hydroxyprogesterone (17\u2010OHP) and the risk of being compound heterozygous for severe mutations in children with non\u2010classical 21\u2010hydroxylase deficiency (NC21OHD). <jats:italic>Methods<\/jats:italic>: In 86 Spanish NC21OHD children (75 families) an analysis of the 21\u2010hydroxylase (21\u2010OH) gene was performed by CYP21B\u2010specific polymerase chain reaction amplification, allele\u2010specific oligonucleotide hybridization and Southern blotting. Familial analysis established how the alleles segregated, and allowed the selection of 21\u2010OH\u2010genotyped normal and carrier children, which proved useful in determining a more precise definition of the cut\u2010off for diagnosis. Receiver operating characteristics (ROC) curve analyses were performed to determine the potential value of 17\u2010OHP in predicting compound heterozygosity for severe mutations. <jats:italic>Results<\/jats:italic>: Thirty\u2010four of the 86 children (39%) were found to carry one severe 21\u2010OH mutation (7.3% deletions or conversions, 2.7% 655G, 2.7% Q318X, 1.3% I172N, 1.3% R356W, and 3.3% double microconversions or small conversions involving single exons). The predominant mutation was V281L (56.7%). P453S and P30L were less frequent (3.3 and 2%). No patient showed two severe mutations. The degree of enzymic deficiency, as measured by basal or adrenocorticotropic hormone (ACTH)\u2010stimulated 17\u2010OHP levels in fully genotyped patients, but not clinical severity (age and number of symptoms at diagnosis), was found to be significantly greater in children with the severe\/mild genotype. ROC curve analyses revealed a strong association between ACTH\u201017\u2010OHP and genotype (area under the curve 0.908, SE 0.057).<\/jats:p><jats:p> <jats:italic>Conclusion<\/jats:italic>: ACTH\u2010stimulated 17\u2010OHP may predict the risk of severe mutations in compound heterozygosity in children (maximum predictive value 93% sensitivity and 83% specificity for a cut\u2010off at 151 nmol 1<jats:sup>\u20101<\/jats:sup>), although a certain overlap in individual values is observed and performance of molecular analysis should never be obviated in the genetic counselling of these patients.<\/jats:p>","DOI":"10.1111\/j.1651-2227.2002.tb02851.x","type":"journal-article","created":{"date-parts":[[2010,8,6]],"date-time":"2010-08-06T23:41:00Z","timestamp":1281138060000},"page":"892-898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Non\u2010classical 21\u2010hydroxylase deficiency in children: association of adrenocorticotropic hormone\u2010stimulated 17\u2010hydroxyprogesterone with the risk of compound heterozygosity with severe mutations"],"prefix":"10.1111","volume":"91","author":[{"given":"B","family":"Ezquieta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Cueva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Jariego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,1,2]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.78.4.810"},{"key":"e_1_2_1_3_2","first-page":"4077","volume-title":"The metabolic and molecular bases of inherited disease","author":"Donohue PA","year":"2001"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.21.3.245"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2000.00995.x"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1430397"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115897"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00207379"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.78.5.1145"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.5.1505"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.4.e68"},{"key":"e_1_2_1_12_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1210\/jcem.86.1.7131","article-title":"Phenotype\u2010genotype correlation in 56 women with non\u2010classical congenital adrenal hyperplasia due to 21\u2010hydroxylase deficiency","volume":"86","author":"Deneux C","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3036"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-195909000-00030"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1093\/clinchem\/42.7.1108","article-title":"Non\u2010isotopic detection of point mutations in the CYP21B gene in 21\u2010hydroxylase deficiency","volume":"42","author":"Ezquieta B","year":"1996","journal-title":"Clin Chem"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000023346"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199705)17:5<429::AID-PD77>3.0.CO;2-9"},{"key":"e_1_2_1_18_2","unstructured":"EzquietaB CuevaE OyarzabalM OliverA VarelaJM JariegoC.Different mechanisms contribute to the most frequent severe point mutations in congenital adrenal hyperplasia (21\u2010hydroxy\u2010lase deficiency) in the Spanish population: gene conversion (655G splicing mutation) and founder effect (Gln318Stop). Clin Genet (in press)."},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004390051046"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.1.378"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1997.2632"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.2.479"}],"container-title":["Acta Paediatrica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1651-2227.2002.tb02851.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1651-2227.2002.tb02851.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T14:23:48Z","timestamp":1700317428000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1651-2227.2002.tb02851.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,8]]},"references-count":21,"aliases":["10.1080\/080352502760148595"],"journal-issue":{"issue":"8","published-print":{"date-parts":[[2002,8]]}},"alternative-id":["10.1111\/j.1651-2227.2002.tb02851.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1651-2227.2002.tb02851.x","archive":["Portico"],"relation":{},"ISSN":["0803-5253","1651-2227"],"issn-type":[{"value":"0803-5253","type":"print"},{"value":"1651-2227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,8]]},"assertion":[{"value":"2007-01-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}