{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:18:41Z","timestamp":1791944321733,"version":"4.3.4"},"reference-count":33,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders. CAH is most often caused by deficiency of steroid 21-hydroxylase. The frequency of CYP21-inactivating mutations and the genotype-phenotype relationship were characterized in 155 well defined unrelated CAH patients. We were able to elucidate 306 of 310 disease-causing alleles (diagnostic sensitivity, 98.7%). The most frequent mutation was the intron 2 splice site mutation (30.3%), followed by gene deletions (20.3%), the I172N mutation (19.7%) and large gene conversions (7.1%). Five point mutations were detected that have not been described in other CAH cohorts. Genotypes were categorized in 4 mutation groups (null, A, B, and C) according to their predicted functional consequences and compared to the clinical phenotype. The positive predictive value for null mutations (ppvnull) was 100%, as all patients with these mutations had a salt-wasting phenotype. In mutation group A (intron 2 splice site mutation in homozygous or heterozygous form with a null mutation), the ppvA to manifest with salt-wasting CAH was 90%. In group B predicted to result in simple virilizing CAH (I172N in homozygous or compound heterozygous form with a more severe mutation), ppvB was 74%. In group C (P30L, V281L, P453S in homozygous or compound heterozygous form with a more severe mutation), ppvC was 64.7% to exhibit the nonclassical form of CAH, but 90% when excluding the P30L mutation. Thus, in general, a good genotype-phenotype relationship is shown in patients with either the severest or the mildest mutations. A considerable degree of divergence is observed within mutation groups of intermediate severity. As yet undefined factors modifying 21-hydroxylase gene expression and steroid hormone action are likely to account for these differences in phenotypic expression.<\/jats:p>","DOI":"10.1210\/jcem.85.3.6441","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T12:05:19Z","timestamp":1389182719000},"page":"1059-1065","source":"Crossref","is-referenced-by-count":295,"title":["Predicting Phenotype in Steroid 21-Hydroxylase Deficiency? Comprehensive Genotyping in 155 Unrelated, Well Defined Patients from Southern Germany"],"prefix":"10.1210","volume":"85","author":[{"given":"Nils","family":"Krone","sequence":"first","affiliation":[{"name":"University Children\u2019s Hospital, Ludwig Maximilians University, D-80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Braun","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ludwig Maximilians University, D-80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelbert Anton","family":"Roscher","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ludwig Maximilians University, D-80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"Knorr","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ludwig Maximilians University, D-80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Peter","family":"Schwarz","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Ludwig Maximilians University, D-80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614105273700_R1","first-page":"2929","volume":"7","author":"Donohoue","year":"1995"},{"key":"2020071614105273700_R2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/humu.1380030408","article-title":"Mutations in steroid 21-hydroxylase (CYP21).","volume":"3","author":"White","year":"1994","journal-title":"Hum Mutat"},{"key":"2020071614105273700_R3","first-page":"650","article-title":"High frequency of nonclassical steroid 21-hydroxylase deficiency.","volume":"37","author":"Speiser","year":"1985","journal-title":"Am J Hum Genet"},{"key":"2020071614105273700_R4","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1073\/pnas.82.4.1089","article-title":"Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man.","volume":"82","author":"White","year":"1985","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614105273700_R5","doi-asserted-by":"crossref","first-page":"5111","DOI":"10.1073\/pnas.83.14.5111","article-title":"Structure of human steroid 21-hydroxylase genes.","volume":"83","author":"White","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614105273700_R6","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1073\/pnas.83.9.2841","article-title":"Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene.","volume":"83","author":"Higashi","year":"1986","journal-title":"Proc Natl Acad Sci 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