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http://purl.uniprot.org/citations/10720040http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10720040http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10720040http://www.w3.org/2000/01/rdf-schema#comment"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 (ppv(null)) 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 ppv(A) 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), ppv(B) was 74%. In group C (P30L, V281L, P453S in homozygous or compound heterozygous form with a more severe mutation), ppv(C) 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."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.org/dc/terms/identifier"doi:10.1210/jcem.85.3.6441"xsd:string
http://purl.uniprot.org/citations/10720040http://purl.org/dc/terms/identifier"doi:10.1210/jcem.85.3.6441"xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Schwarz H.P."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Schwarz H.P."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Braun A."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Braun A."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Roscher A.A."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Roscher A.A."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Knorr D."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Knorr D."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Krone N."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/author"Krone N."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/name"J. Clin. Endocrinol. Metab."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/name"J. Clin. Endocrinol. Metab."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/pages"1059-1065"xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/pages"1059-1065"xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/title"Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well defined patients from southern Germany."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/title"Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well defined patients from southern Germany."xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/volume"85"xsd:string
http://purl.uniprot.org/citations/10720040http://purl.uniprot.org/core/volume"85"xsd:string
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