CoChat
Sign Up
Cited by 108Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

Molecular Genotyping in Brazilian Patients with the Classical and Nonclassical Forms of 21-Hydroxylase Deficiency1

Bachega, Tânia A. S. S., Billerbeck, Ana Elisa C., Madureira, Guiomar, Marcondes, José A. M., Longui, Carlos A., Leite, Maristela V., Arnhold, Ivo J. P., Mendonca, Berenice B.·1998·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.83.12.5350
Open this paper in CoChat — free account

Abstract

The aim of our study was to determine, by allele-specific PCR, the frequency of point mutations in 130 Brazilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency and to correlate genotype with phenotype. The most frequent mutations were 12 splice (41.8% in salt wasting), I172N (32.6% in simple virilizing), and V281L (40.2% in late onset form). The frequency of the 9 most common point mutations was similar to that reported for other countries, except for Del 8 nt and Cluster, which were less frequent in the classical form. Rarer mutations such as P453S, G291S, I7 splice, W405X, R483P, and R483-->frameshift were rarely found or were absent. The 93 fully genotyped patients were classified into 3 mutation groups, based on the degree of enzymatic activity (group A, <2%; group B, approximately 2%, and group C, >18%). In group A, 62% of the cases presented the salt wasting form; in group B, 96% the simple virilizing form; and in group C, 88% the late onset form. We diagnosed 80% of the affected alleles after screening for large rearrangements and 15 point mutations. The absence of previously described mutations in 20% of the affected alleles suggests the presence of new mutations in our population.

Integrity signals

Registry

Crossref · 10.1210/jcem.83.12.5350

Cites

21 of 21 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?

  • High homology and tandem configuration make the RCCX region prone to meiotic misalignment, fostering recurrent recombination through unequal crossover and gene conversion, which are the predominant mechanisms underlying pathogenic variants in 21-OHD.

    “The abovementioned high degree of homology and tandem configuration make this region particularly prone to meiotic misalignment, which fosters recurrent recombination through unequal crossover and gene conversion. These processes constitute the predominant mechanisms underlying pathogenic variants in 21-OHD (16–19).”

    From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [18]

  • 90-95% of pathogenic CYP21A2 variants arise from intergenic recombination between the active gene and its pseudogene within the RCCX module.

    “Overall, 90–95% of pathogenic CYP21A2 variants arise from intergenic recombination between the active gene and its pseudogene within the RCCX module.”

    From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [18]

  • Functional in vitro studies classify CYP21A2 pathogenic variants into four groups based on residual enzymatic activity: group 0 (null, 0%), group A (<2%), group B (3-7%), and group C (20-60%).

    “Functional in vitro studies have allowed classification of CYP21A2 pathogenic variants into four groups based on residual enzymatic activity: group 0 (null, 0%), group A (<2%), group B (3-7%), and group C (20-60%), as summarized in Table 1 (18, 31, 48–50).”

    From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [18]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Bachega, T. A. S. S., Billerbeck, A. E. C., Madureira, G., Marcondes, J. A. M., Longui, C. A., Leite, M. V., Arnhold, I. J. P., & Mendonca, B. B.
Affiliations
  • Universidade de São Paulo (BR)
  • Irmandade da Santa Casa de Misericórdia de São Paulo (BR)
  • Universidade Federal do Rio Grande do Norte (BR)
Corresponding author
Mendonca, Berenice B.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1998-12
Volume
83
Issue
12
Pages
4416-4419
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.83.12.5350
OpenAlex
W2059566069
Cited by
108
References
21
Citations by year
2026: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 1 · 2013: 4 · 2012: 6
FWCI
1.17
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Strong
  • Fundação de Amparo à Pesquisa do Estado de São Paulo
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
21-hydroxylase deficiency, CYP21A2 mutations, point mutations, splice site mutation, genotype-phenotype correlation, salt wasting, late onset, novel mutations, mutation frequency, Brazilian patients
MeSH terms
Adrenal Hyperplasia, Congenital, Alleles, Brazil, Female, Gene Frequency, Genotype, Humans, Male, Phenotype, Steroid 21-Hydroxylase, Cohort Studies, 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