{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:52:15Z","timestamp":1745470335180,"version":"3.40.4"},"reference-count":29,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2008,11,27]],"date-time":"2008-11-27T00:00:00Z","timestamp":1227744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2008,11,27]],"date-time":"2008-11-27T00:00:00Z","timestamp":1227744000000},"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":[[2009]]},"abstract":"<jats:p>&lt;i&gt;Aims:&lt;\/i&gt; Hyperandrogenism, although mostly due to polygenic interactions, is monogenic for some enzymatic adrenal deficiencies. This study evaluates mono- and biallelic 21-hydroxylase deficiency (21OHD)-related hyperandrogenism in pediatric patients. Sensitizing and protective polymorphisms were investigated in carriers and cryptic forms of 21OHD. &lt;i&gt;Methods:&lt;\/i&gt; The study involved a monogenic analysis of CYP21A2 in patients (375 nonclassical 21OHD [NC21OHD] children; 306 hyperandrogenic 21OHD carriers, n = 306) and a polygenic association study (CAPN10-UCSNP44, PON1-108, TNFR2-M196R, IGF2-ApaI and IRS1-G972R polymorphisms) of 170 hyperandrogenic carriers plus 277 family members (control groups). The metabolic marker 17OH progesterone defined the degree of deficiency; clinical expressivity was determined by pediatric endocrinologists. &lt;i&gt;Results:&lt;\/i&gt; The group of 21OHD carriers manifesting hyperandrogenism was enriched in the CAPN-UCSNP44 rare variant in homozygosity (4.9 vs. 0.4%, NCBI data for the general population; p = 0.004). In our patients and controls, contrasting distributions were observed for this and another polymorphism, TNFR2-196R. In a recessive model, their rare variants were more frequently detected among the forms with high (p = 0.048) and low (p = 0.034) expressivity respectively. &lt;i&gt;Conclusions:&lt;\/i&gt; 21OHD-related pediatric hyperandrogenism follows monogenic and polygenic models. The opposite behaviors in terms of clinical expressivity detected for CAPN-UCSNP44 and TNFR2-M196R rare variants suggest these variants to be sensitizing and protective factors respectively in adrenal hyperandrogenism.<\/jats:p>","DOI":"10.1159\/000173739","type":"journal-article","created":{"date-parts":[[2008,11,29]],"date-time":"2008-11-29T14:20:02Z","timestamp":1227968402000},"page":"28-37","source":"Crossref","is-referenced-by-count":6,"title":["Monogenic and Polygenic Models Detected in Steroid 21-Hydroxylase Deficiency-Related Paediatric Hyperandrogenism"],"prefix":"10.1159","volume":"71","author":[{"given":"B.","family":"Ezquieta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Oyarzabal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Barrio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Luzuriaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Hermoso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.L.","family":"Lechuga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Quinteiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.I.","family":"Labarta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Gutierrez 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