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Published on: July 14, 2016
Variable phenotypes associated with aromatase (CYP19) insufficiency in humans
Lin Lin1, Oya Ercan, Jamal Raza
1Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.
The Journal of Clinical Endocrinology and Metabolism
|December 14, 2006
Summary
Aromatase (CYP19) gene mutations can cause varied "nonclassic" phenotypes in 46,XX individuals, leading to differences in puberty and development. Low residual enzyme activity may support some estrogen-dependent development.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Aromatase (CYP19) is essential for estrogen biosynthesis from androgens.
- Complete aromatase deficiency causes genital ambiguity and absent puberty in 46,XX individuals.
- The existence of nonclassic aromatase insufficiency phenotypes was previously unknown.
Observation:
- Four 46,XX patients from three kindreds presented with variable androgenization and pubertal failure.
- Mutational analysis of CYP19 and enzyme activity assays were performed.
- Patients exhibited diverse clinical presentations, from genital ambiguity to pubertal failure.
Findings:
- Specific CYP19 mutations (R435C, F234del, exon5del) were identified in patients.
- Genital ambiguity with variable pubertal breast development was observed in patients with point mutations or small deletions.
- A patient with a larger deletion (exon5del) showed absent puberty and minimal androgenization.
- Low residual aromatase activity correlated with some breast development during puberty.
Implications:
- Aromatase gene mutations can result in variable, nonclassic phenotypes.
- Residual aromatase activity can be sufficient for some estrogen-dependent development (e.g., breast, uterus) at puberty.
- Phenotypic variability may be influenced by other genetic or environmental factors affecting estrogen synthesis or action.
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