Lack of genotypephenotype correlation in congenital adrenal hyperplasia due to a CYP21A2-like gene.

Clinica chimica acta; international journal of clinical chemistry

PubMedID: 25025300

Leccese A, Longo V, Dimatteo C, De Girolamo G, Trunzo R, D'Andrea G, Bafunno V, Margaglione M, Santacroce R. Lack of genotypephenotype correlation in congenital adrenal hyperplasia due to a CYP21A2-like gene. Clin Chim Acta. 2014;43748-51.
CONTEXT
Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, encoded by CYP21A2 gene, is an autosomal recessive disorder. The CYP21A2 gene, localized in a genetic unit defined RCCX module, is considered one of the most polymorphic of human genes.

OBJECTIVES
We considered new evidences about the presence of a RCCX trimodular haplotype with a CYP21A2-like gene to explain the lack of a genotype-phenotype correlation in individuals of two different families.

DESIGN AND METHODS
To verify gene duplication we used Multiplex Ligation Probe-Dependent Amplifications (MLPA) and to confirm the presence of a CYP21A2-like gene downstream TNXA gene we used previously described amplification and restriction strategy followed by the sequencing of the CYP21A2 gene downstream TNXB gene.

RESULTS
The amplification strategy and restriction analysis of CYP21A1P/CYP21A2-TNXA PCR product in association with MLPA assay and sequencing of CYP21A2 gene downstream TNXB were able to identify the presence of the CYP21A2-like gene in healthy subjects of the two families, wherein the direct sequencing of CYP21A2 gene showed genotypes correlated to pathological phenotypes.

CONCLUSIONS
The strategy suggested is useful to facilitate molecular testing in CAH patients, considering the new evidence about possible different haplotypes.