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dc.contributor.author Dolzan V
dc.contributor.author Sólyom, János
dc.contributor.author Fekete, György
dc.contributor.author Kovacs J
dc.contributor.author Rakosnikova V
dc.contributor.author Votava F
dc.contributor.author Lebl J
dc.contributor.author Pribilincova Z
dc.contributor.author Baumgartner-Parzer SM
dc.contributor.author Riedl S
dc.contributor.author Waldhauser F
dc.contributor.author Frisch H
dc.contributor.author Stopar-Obreza M
dc.contributor.author Krzisnik C
dc.contributor.author Battelino T
dc.date.accessioned 2018-07-27T07:03:33Z
dc.date.available 2018-07-27T07:03:33Z
dc.date.issued 2005
dc.identifier 22744441059
dc.identifier.citation pagination=99-106; journalVolume=153; journalIssueNumber=1; journalTitle=EUROPEAN JOURNAL OF ENDOCRINOLOGY;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/4984
dc.identifier.uri doi:10.1530/eje.1.01944
dc.description.abstract OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.
dc.relation.ispartof urn:issn:0804-4643
dc.title Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia
dc.type Journal Article
dc.date.updated 2018-02-22T10:31:48Z
dc.language.rfc3066 en
dc.identifier.mtmt 1754496
dc.identifier.wos 000230677400013
dc.identifier.pubmed 15994751
dc.contributor.department SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika
dc.contributor.institution Semmelweis Egyetem


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