CoChat
Sign Up
Cited by 96Sexual Differentiation and DisordersAdrenal Hormones and DisordersOvarian function and disorders

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia

Dolž;an, V, Sólyom, J, Fekete, G, Kovács, J, Rakosnikova, V, Votava, F, Lebl, J, Pribilincova, Z +7 more·2005·European Journal of Endocrinology
DOI 10.1530/eje.1.01944
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1530/eje.1.01944

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In European and North American populations, large gene deletions and CYP21A1P/CYP21A2 chimeric conversions, predominantly associated with salt-wasting phenotypes, constitute 20-30% of pathogenic alleles.

    “In European and North American population, where long-standing newborn screening programs facilitate early detection, large gene deletions and CYP21A1P/CYP21A2 chimeric conversions, predominantly associated with SW phenotypes, constitute 20-30% of pathogenic alleles (25, 28, 30, 31).”

    From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [30]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Dolž;an, V, Sólyom, J., Fekete, G., Kovács, J., Rakosnikova, V, Votava, F., Lebl, J., Pribilincova, Z., Baumgartner-Parzer, S., Riedl, S., Waldhauser, F., Frisch, H., Stopar-Obreza, M., Krž;išnik, C., & Battelino, T.
Affiliations
Semmelweis University (HU)
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2005-07
Volume
153
Issue
1
Pages
99-106
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje.1.01944
OpenAlex
W2165157670
Cited by
96
References
7
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 7 · 2017: 7 · 2016: 8 · 2015: 2 · 2014: 9 · 2013: 5 · 2012: 10
FWCI
1.37
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Semmelweis University Repository (Semmelweis University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Keywords
congenital adrenal hyperplasia, CYP21, 21-hydroxylase, mutation spectrum, genotype-phenotype correlation, 17-hydroxyprogesterone, mutation detection
MeSH terms
Adrenal Hyperplasia, Congenital, Child, Europe, Eastern, Female, Gene Frequency, Genetic Counseling, Genetic Testing, Genotype, Humans, Male, Phenotype, Steroid 21-Hydroxylase, Gene Deletion, Point Mutation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review