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http://purl.uniprot.org/citations/12222711http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12222711http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12222711http://www.w3.org/2000/01/rdf-schema#comment"

Aim

To investigate the association between levels of 17-hydroxyprogesterone (17-OHP) and the risk of being compound heterozygous for severe mutations in children with non-classical 21-hydroxylase deficiency (NC21OHD).

Methods

In 86 Spanish NC21OHD children (75 families) an analysis of the 21-hydroxylase (21-OH) gene was performed by CYP21B-specific polymerase chain reaction amplification, allele-specific oligonucleotide hybridization and Southern blotting. Familial analysis established how the alleles segregated, and allowed the selection of 21-OH-genotyped normal and carrier children, which proved useful in determining a more precise definition of the cut-off for diagnosis. Receiver operating characteristics (ROC) curve analyses were performed to determine the potential value of 17-OHP in predicting compound heterozygosity for severe mutations.

Results

Thirty-four of the 86 children (39%) were found to carry one severe 21-OH mutation (7.3% deletions or conversions, 2.7% 655G, 2.7% Q318X, 1.3% 1172N, 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)-stimulated 17-OHP 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-17-OHP and genotype (area under the curve 0.908, SE 0.057).

Conclusion

ACTH-stimulated 17-OHP may predict the risk of severe mutations in compound heterozygosity in children (maximum predictive value 93% sensitivity and 83% specificity for a cut-off at 151 nmol l(-1)), 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."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.org/dc/terms/identifier"doi:10.1080/080352502760148595"xsd:string
http://purl.uniprot.org/citations/12222711http://purl.org/dc/terms/identifier"doi:10.1080/080352502760148595"xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Fernandez J."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Fernandez J."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Varela J."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Varela J."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Oliver A."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Oliver A."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Cueva E."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Cueva E."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Ezquieta B."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Ezquieta B."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Jariego C."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/author"Jariego C."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/name"Acta Paediatr."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/name"Acta Paediatr."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/pages"892-898"xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/pages"892-898"xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/title"Non-classical 21-hydroxylase deficiency in children: association of adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk of compound heterozygosity with severe mutations."xsd:string
http://purl.uniprot.org/citations/12222711http://purl.uniprot.org/core/title"Non-classical 21-hydroxylase deficiency in children: association of adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk of compound heterozygosity with severe mutations."xsd:string
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