CoChat
Sign Up
Cited by 397Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

The DOI matches its Crossref record; 36 of the 49 references it cites were found in a registry or an index.

Predicting Phenotype in Steroid 21-Hydroxylase Deficiency? Comprehensive Genotyping in 155 Unrelated, Well Defined Patients from Southern Germany

Krone, Nils, Braun, Andreas, Roscher, Adelbert Anton, Knorr, Dietrich, Schwarz, Hans Peter·2000·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.85.3.6441
Open this paper in CoChat — free account

Abstract

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.

Overview

Integrity signals

Registry

Crossref · 10.1210/jcem.85.3.6441

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

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

Verification

Claims the paper makes

This paper’s full text isn’t openly available, 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?

Citations

Cites

Show all 49 references

Research works printed but not linked: 1

  1. Donohoue, 1995, 7, 2929

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Krone, N., Braun, A., Roscher, A. A., Knorr, D., & Schwarz, H. P.
Affiliations
Ludwig-Maximilians-Universität München (DE)
Corresponding author
Schwarz, Hans Peter
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2000-03-01
Volume
85
Issue
3
Pages
1059-1065
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.85.3.6441
OpenAlex
W2066497061
Semantic Scholar
a988cc456aad7cb2ff501db38740a080992699c6
Cited by
397
References
49
Citations by year
2026: 9 · 2025: 13 · 2024: 10 · 2023: 15 · 2022: 9 · 2021: 27 · 2020: 17 · 2019: 21 · 2018: 10 · 2017: 11 · 2016: 25 · 2015: 12 · 2014: 19 · 2013: 21 · 2012: 16
FWCI
3.62
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
congenital adrenal hyperplasia, 21-hydroxylase deficiency, CYP21, genotype-phenotype correlation, CYP21 mutations, salt-wasting phenotype, compound heterozygosity, gene conversion, positive predictive value
MeSH terms
Adrenal Hyperplasia, Congenital, Alleles, DNA Mutational Analysis, Gene Frequency, Genotype, Germany, Humans, Mutation, Phenotype, Predictive Value of Tests, Steroid 21-Hydroxylase, Cohort Studies

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