Endocrine profile and phenotype-genotype correlation in unrelated patients with non-classical congenital adrenal hyperplasia

Clin Biochem. 2011 Aug;44(12):959-63. doi: 10.1016/j.clinbiochem.2011.05.013. Epub 2011 May 24.

Abstract

Objectives: The aim of this study was to identify the molecular defect in a group of 37 unrelated Greek Cypriot patients affected by NC-CAH and evaluate the relationship between the genotype, phenotype and adrenal androgen levels.

Design and methods: Clinical evaluation, biochemical analysis of 17-OHP, Testosterone, Androstenedione, DHEA-S, direct DNA sequencing and MLPA analyses.

Results: Eleven known mutations were identified with the p.V281L being the most predominant and observed in 68.9% of the alleles. There was no difference between the two genotypes (mild/mild and mild/severe) with clinical presentation, whereas a proportional relationship between the type of mutation and adrenal androgen levels was found.

Conclusion: The frequency of the underlying genetic defect in our patients with NC-CAH is similar to that observed in most Mediterranean populations. Although the genotype cannot solely explain the clinical expression of NC-CAH, discrimination between mild and severe alleles is crucial in antenatal diagnosis and genetic counselling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-alpha-Hydroxyprogesterone / blood
  • Adolescent
  • Adrenal Hyperplasia, Congenital / diagnosis
  • Adrenal Hyperplasia, Congenital / genetics*
  • Adult
  • Androstenedione / blood
  • Child
  • Cyprus
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Haplotypes
  • Humans
  • Male
  • Mutation
  • Severity of Illness Index
  • Steroid 21-Hydroxylase / genetics*
  • Testosterone / blood

Substances

  • Testosterone
  • Androstenedione
  • 17-alpha-Hydroxyprogesterone
  • Steroid 21-Hydroxylase