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Cited by 55Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

High variability in CYP21A2 mutated alleles in Spanish 21‐hydroxylase deficiency patients, six novel mutations and a founder effect

Loidi, Lourdes, Quinteiro, Celsa, Parajes, Silvia, Barreiro, Jesús, Lestón, Domingo G., Cabezas‐Agrícola, José M., Sueiro, Aurelio M., Araujo‐Vilar, David +4 more·2006·Clinical Endocrinology
DOI 10.1111/j.1365-2265.2006.02465.x
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Abstract

Summary: Objective To detect common as well as rare and novel CYP21A mutations in 21‐hydroxylase deficiency patients. To estimate the distribution of mutations and compare them with other European studies. To construct haplotypes linked to a recurrent novel mutation. Design Genetic analysis by sequencing the entire CYP21A2 gene plus Southern blot. Patients A total of 138 unrelated Spanish patients: 122 nonclassical forms (NCF) and 16 classical forms (CF) were studied. Results Among the 266 nonrelated mutated alleles; CYP21A2 deletions/conversions and a spectrum of 27 different mutated alleles were found: 15 different single point mutations, 8 nucleotide deletions in exon 3, 3 mutation clusters in exon 6, 9 alleles with more than one mutation, one 21‐nucleotide duplication in exon 10, and one allele with CYP21A2 duplicated and both copies mutated. The most frequent mutation in NCF alleles is V281L (71·8%). Among CFs, the most common is I2 g (20%) and Q318X (16%) and rare alleles (21·9%). Six novel causative mutations were found, four associated with CF: I46+1nt, R444X, P463L and M473_R479dup and two associated with NCF: W302 and D322G. The R444X mutation was found in seven unrelated patients and it appeared only once in an ancestral haplotype. In addition, we found a novel single nucleotide polymorphism with a 31·5% frequency for the rare allele. Conclusion A great diversity of haplotypes with a large spectrum of mutated alleles was found. The frequency of the V281L mutation was the highest reported and the relatively high frequency of R444X was the result of a founder effect.

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  • Population-based studies reveal rare or population-specific alleles, highlighting extensive allelic heterogeneity of 21-OHD and the necessity of using ethnically tailored genetic panels for accurate diagnosis and effective genetic counseling.

    “Nevertheless, population-based studies continue to reveal rare or population-specific alleles, highlighting the extensive allelic heterogeneity of 21-OHD and the necessity of using ethnically tailored genetic panels for accurate diagnosis and effective genetic counseling (5, 16, 19, 22, 28, 33–35).”

    From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [34]

  • 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 [202]

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Authors
Loidi, L., Quinteiro, C., Parajes, S., Barreiro, J., Lestón, D. G., Cabezas‐Agrícola, J. M., Sueiro, A. M., Araujo‐Vilar, D., Catro‐Feijóo, L., Costas, J., Pombo, M., & Domínguez, F.
Affiliations
  • Complejo Hospitalario Universitario de Santiago (ES)
  • Universidade de Santiago de Compostela (ES)
Corresponding author
Loidi, Lourdes
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2006-02-09
Volume
64
Issue
3
Pages
330-336
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/j.1365-2265.2006.02465.x
OpenAlex
W1996974219
Cited by
55
References
3
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 5
FWCI
1.62
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
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, novel mutations, founder effect, haplotypes, single nucleotide polymorphisms, mutation spectrum, Spanish patients
MeSH terms
Adrenal Hyperplasia, Congenital, Alleles, Base Sequence, Family Health, Female, Gene Conversion, Gene Frequency, Haplotypes, Humans, Male, Mutation, Phenotype, Steroid 21-Hydroxylase, Gene Deletion, Point Mutation, Gene Duplication, Polymorphism, Single Nucleotide

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