CoChat
Sign Up
Cited by 63Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

CYP21A2 mutations in Portuguese patients with congenital adrenal hyperplasia: identification of two novel mutations and characterization of four different partial gene conversions

Friães, Ana, Rêgo, Ana Toste, Aragüés, José Maria, Moura, Luís Francisco, Mirante, Alice, Mascarenhas, Mário Rui, Kay, Teresa Taylor, Lopes, Lurdes Afonso +5 more·2006·Molecular Genetics and Metabolism
DOI 10.1016/j.ymgme.2005.11.015
Open this paper in CoChat — free account

Abstract

More than 90% of congenital adrenal hyperplasia (CAH) cases are caused by 21-hydroxylase deficiency. In this study, the CYP21 gene was genotyped in 56 Portuguese unrelated patients with clinical symptoms of 21-hydroxylase deficiency, in a total of 112 independent alleles. CYP21A2 mutations were identified in 99.1% of the alleles. The most common point mutation was 1688G>T (25.9%). A previously unreported partial gene conversion, extending from exon 1 to 7, was found in 16.1% of the alleles, in most cases associated to the mutation 1688G>T in the other chromosome, and in patients with nonclassical CAH. Other three distinct partial gene conversions were also identified, with lower frequencies: one extends from exon 1 to 3 and the others from exons 3 to 7 and 3 to 8. Two novel mutations were identified in two salt-wasting patients: a putative splicing mutation, IVS2+5G>A, and the transition 2557C>T, that gives rise to the nonsense mutation R445X. Seven point mutations and a partial gene conversion were responsible for 88 of the studied disease causing alleles, and the overall concordance between genotype and phenotype was 92.9%. With this study the molecular basis of CAH was characterized, for the first time, in Portuguese patients, providing useful results for clinicians in terms of prediction of disease severity, genetic and prenatal counseling.

Integrity signals

Registry

Crossref · 10.1016/j.ymgme.2005.11.015

Cites

6 of 6 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 a large Brazilian cohort, nine novel or rare variants were identified, several of which exhibited clear founder effects and shared haplotypes with Spanish and Portuguese patients.

    “In a large Brazilian cohort, nine novel or rare variants were identified, several of which (p.(Arg408Cys), c.1450_1451insC, p.(His365Tyr), c.293-2C>G, p.(Gly424Ser) exhibited clear founder effects and shared haplotypes with Spanish and Portuguese patients, reflecting the historical Iberian contribution to Brazilian ancestry (22, 27, 40, 41).”

    From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [40]

  • Deletions, the splice site mutation in intron 2 (c.293-13A/C>G) and p.Ile172Asn (I172N) are the most common mutations in most populations.

    “Deletions, the splice site mutation in intron 2 (c.293-13A/C>G) and p.Ile172Asn (I172N) are the most common mutations in most populations (189,195-213).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [203]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Friães, A., Rêgo, A. T., Aragüés, J. M., Moura, L. F., Mirante, A., Mascarenhas, M. R., Kay, T. T., Lopes, L. A., Rodrigues, J. C., Guerra, S., Dias, T., Teles, A. G., & Gonçalves, J.
Affiliations
  • National Institute of Health Dr. Ricardo Jorge (PT)
  • Hospital de Santa Maria (PT)
  • Unidade Local de Saúde de Coimbra (PT)
  • University of Lisbon (PT)
  • Hospital de Dona Estefânia (PT)
  • Hospital Maria Pia (PT)
Corresponding author
Gonçalves, João
ORCID
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2006-05
Volume
88
Issue
1
Pages
58-65
ISSN
1096-7192 (ISSN-L)
DOI
10.1016/j.ymgme.2005.11.015
OpenAlex
W2096113772
Cited by
63
References
6
Citations by year
2026: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 5
FWCI
2.04
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular Genetics and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Fundação para a Ciência e a Tecnologia
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
congenital adrenal hyperplasia, 21-hydroxylase deficiency, CYP21A2 mutations, novel mutations, splicing mutation, nonsense mutation, genotype-phenotype concordance, salt-wasting CAH, Portuguese patients
MeSH terms
Adrenal Hyperplasia, Congenital, Female, Gene Conversion, Genotype, Humans, Infant, Newborn, Mutation, Phenotype, Portugal, Steroid 21-Hydroxylase, 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