Salt-wasting congenital adrenal hyperplasia: Detection of mutations in CYP21B gene in a Chilean population1
Abstract
The steroid 21-hydroxylase deficiency (21OHD) is the most frequent cause of congenital adrenal hyperplasia. We have characterized the disease-causing mutations in the 21-hydroxylase genes of 63 patients with salt-wasting congenital adrenal hyperplasia from a Chilean population of Hispanic origin, a group that has been scarcely evaluated. Using allele-specific PCR, lesions were identified in 97 chromosomes out of 126 tested (77%). The most frequent findings were the gene deletion or large gene conversion (LGC) = 22.9%, I2 splice = 19%, R357W = 12.7%, and Q319X = 10.5%. We did not find alleles with the mutation F308insT and we found three alleles with the cluster E6. The frequency of the point mutation R357W was at least two times more frequent than the one found in Caucasians populations, but similar to that communicated in Asian populations; this finding may be explained by the Asian ancestry of our South-Amerindian population. The frequency of Q319X was also high, similar only to those patients studied in Italy and in a neighboring Argentinian population. In summary, this is a genetic characterization of 21OHD made in an almost pure Hispanic population in Latin America. The high frequency of deletion of CYP21B gene, I2 splice, R357W, and Q319X mutations probably reflects the European-Caucasian-Spanish influence of the conquerors, mixed with Amerindians of Asian ancestry and modulated by other European immigrations.
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In most populations, targeted genotyping methods achieve a detection rate of approximately 90-95% of known pathogenic alleles.
“In most populations, these methods achieve a detection rate of approximately 90-95% of known pathogenic alleles, providing a balance between analytical precision, efficiency and reproducibility, making it suitable for detecting recurrent CYP21A2 variants in diagnostic laboratories during the 1990s and early 2000s (27, 31, 47, 71, 72).”
From Evolution of molecular diagnostic strategies for 21-hydroxylase deficiency: from classical methods to advanced genomic techniques (2026) · cites this paper as [71]
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- Authors
- Fardella, C. E., Poggi, H., Pineda, P., Soto, J., Torrealba, I., Cattani, A., Oestreicher, E., & Foradori, A.
- Affiliations
- Department of Endocrinology (C.E.F., A.C., E.O.), Santiago, Chile
- The Research and Development Unit of the Associated Unit of Clinical Laboratories (H.P., J.S., A.F.), Faculty of Medicine, Catholic University of Chile, Santiago, Chile;
- Hospital Clínico de la Universidad de Chile (CL)
- Pontificia Universidad Católica de Chile (CL)
- Hospital Luis Calvo Mackenna (CL)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1998-09-01
- Volume
- 83
- Issue
- 9
- Pages
- 3357-3360
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1986068286
- Cited by
- 35
- References
- 35
- Citations by year
- 2023: 1 · 2019: 1 · 2017: 1 · 2016: 3 · 2014: 1 · 2012: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (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
- salt-wasting congenital adrenal hyperplasia, 21-hydroxylase deficiency, genetic mutations, gene deletion, mutation frequency, Hispanic population, Chilean population, genetic ancestry, allele-specific PCR
- MeSH terms
- Adrenal Hyperplasia, Congenital, Alleles, Chile, Female, Genotype, Homozygote, Humans, Male, Mutation, RNA Splicing, Steroid 21-Hydroxylase, Polymerase Chain Reaction, Gene Deletion
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