Steroid 21-hydroxylase deficiency: genotype may not predict phenotype

Wilson, R. C.

doi:10.1210/jc.80.8.2322

Cited by 324Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

Steroid 21-hydroxylase deficiency: genotype may not predict phenotype

Wilson, R. C.·1995·Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.80.8.2322

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Abstract

Steroid 21-hydroxylase deficiency is the most frequent cause of congenital adrenal hyperplasia. We have determined the 21-hydroxylase genotype in 197 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency and assessed phenotypic characteristics based on 1) genital status with respect to virilization in females, 2) ACTH stimulation tests to evaluate the secretion of androgens and 17-hydroxyprogesterone, and 3) salt deprivation tests to precisely describe the phenotype with respect to aldosterone deficiency and salt wasting. After dividing our patients into 26 21-hydroxylase gene mutation-identical groups, we found that, in general, the patient's phenotype matched the severity of the genotype. However, in 13 of these groups, the genotype did not always predict the phenotype, even within families. This study, has demonstrated that the 10 most common mutations observed in the 21-hydroxylase gene result in phenotypes that are not always concordant with the genotype.

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A good correlation is generally observed between CYP21A2 genotype and clinical phenotype, although discrepancies have been reported, especially within intermediate severity groups, making phenotype prediction unreliable.
“Generally, a good correlation is observed between CYP21A2 genotype and clinical phenotype, although some discrepancies have been reported especially within mutation groups of intermediate severity, making phenotype prediction unreliable (14).”
From Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche (2011) · cites this paper as [14]
Approximately 65-75% of CAH patients are compound heterozygotes, and clinical expression correlates with the less severely mutated allele and residual 21-hydroxylase activity.
“Approximately 65-75% of the CAH patients are compound heterozygotes, and the clinical expression correlates with the less severely mutated allele, and, consequently, with the residual activity of 21-OH (14).”
From Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche (2011) · cites this paper as [14]

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Authors: Wilson, R. C.
ORCID: Wilson, R. C.
Venue: Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 1995-08-01
Volume: 80
Issue: 8
Pages: 2322-2329
ISSN: 0021-972X (ISSN-L)
DOI: 10.1210/jc.80.8.2322
OpenAlex: W2014696401
Cited by: 324
References: 0
Citations by year: 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 8 · 2014: 7 · 2013: 10 · 2012: 6
FWCI: 4.09
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Center for Research Resources (RR06020)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 00072)
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, congenital adrenal hyperplasia, genotype-phenotype discordance, 17-hydroxyprogesterone, ACTH stimulation test, aldosterone deficiency, salt wasting
MeSH terms: Adrenal Hyperplasia, Congenital, Adult, Aldosterone, Alleles, Child, Preschool, Female, Genotype, Humans, Infant, Newborn, Male, Mutation, Phenotype, Regression Analysis, Steroid 21-Hydroxylase, Virilism

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Steroid 21-hydroxylase deficiency: genotype may not predict phenotype

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