{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T15:22:41Z","timestamp":1771860161879,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:p>OBJECTIVE: To evaluate whether genotype differences can explain the clinical variability of non-classical steroid 21-hydroxylase deficiency (NC21-OHD) and to determine if genotype is related to ethnic origin. DESIGN: Genotyping for mutations in the steroid 21-hydroxylase (CYP21) gene was performed in 45 unrelated Israeli Jewish patients (nine males) with NC21-OHD (60min 17-hydroxyprogesterone (17-OHP), 45-386nmol\/l) who were referred for evaluation of postnatal virilization or true precocious\/early puberty. Eleven siblings diagnosed through family screening were genotyped as well. METHODS: Patients were divided by genotype into three groups: (A) homozygous or compound heterozygous for the mild mutations (V281L or P30L) (n=29; eight males); (B) compound heterozygous for one mild and one severe mutation (Q318X, I2 splice, I172N) (n=12; no males); (C) mild mutation detected on one allele only (n=4; one male; peak 17-OHP 58-151nmol\/l). We then related the genotype to the ethnic origin, clinical phenotype and hormone level. Since group C was very small, comparisons were made between groups A and B only. RESULTS: At diagnosis, group B tended to be younger (5. 8+\/-3.0 vs 8.1+\/-4.3 years, P=0.09), had greater height SDS adjusted for mid-parental height SDS (1.6+\/-1.1 vs 0.7+\/-1.4, P=0.034), tended to have more advanced bone age SDS (2.9+\/-1.5 vs 1.7+\/-2.1, P=0.10) and had a higher peak 17-OHP level in response to ACTH stimulation (226+\/-92 vs 126+\/-62nmol\/l, P&lt;0.01). Group B also had pubarche and gonadarche at an earlier age (5.1+\/-2.4 vs 7.4+\/-2.2 years, P&lt;0.01 and 7.4+\/-1.8 vs 9.9+\/-1.4 years, P&lt;0.001, respectively) and a higher rate of precocious puberty (50 vs 17%, P=0.04). Stepwise logistic regression analysis (excluding males) yielded age at gonadarche as the most significant variable differentiating the two groups, with a positive predictive value of 86% for a cut-off of 7.5 years. CONCLUSIONS: The findings suggest that genotype might explain some of the variability in the phenotypic expression of NC21-OHD. Compound heterozygotes for one mild and one severe mutation have a higher peak 17-OHP associated with pubarche and gonadarche at an earlier age and more frequent precocious puberty. Hence, the severity of the enzymatic defect might determine the timing and pattern of puberty.<\/jats:p>","DOI":"10.1530\/eje.0.1430397","type":"journal-article","created":{"date-parts":[[2005,1,24]],"date-time":"2005-01-24T21:34:41Z","timestamp":1106602481000},"page":"397-403","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":44,"title":["Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency"],"prefix":"10.1093","author":[{"given":"N","family":"Weintrob","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Brautbar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Pertzelan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z","family":"Josefsberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z","family":"Dickerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Kauschansky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Lilos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Peled","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Phillip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Israel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/143\/3\/397.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/143\/3\/397.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:28:56Z","timestamp":1676392136000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/143\/3\/397\/6750541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1530\/eje.0.1430397","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,9,1]]}}}