Molecular defects of the CYP21A2 gene in Greek-Cypriot patients with congenital adrenal hyperplasia.
OBJECTIVE
To determine the mutations in the CYP21A2 gene in Greek-Cypriots with congenital adrenal hyperplasia (CAH) and attempt a genotype-phenotype correlation.


METHODS
Molecular analysis was performed by multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 32 CAH patients.


RESULTS
The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (55%) mutation, followed by Large lesion (20%) and in the non-classical form, the p.V281L (79.5%). Genotypes were categorized in 4 mutation groups (null, A, B and C). All 3 patients in the null group manifested the salt-wasting form and all 6 patients in mutation group A presented with the classical form. One patient in group B had the simple virilizing form and 22 patients in group C exhibited the non-classical form.


CONCLUSIONS
The spectrum of mutations of the CYP21A2 gene in our population is comparable to the most common reported in similar ethnic groups. The knowledge of the ethnic specificity of the CYP21A2 mutations represents a valuable diagnostic tool for all forms of CAH.
Skordis
Nicos
N
Paediatric Endocrine Unit, Department of Paediatrics, Makarios Hospital, Nicosia, Cyprus. nskordis@cytanet.com.cy
Kyriakou
Andreas
A
Tardy
Véronique
V
Ioannou
Yiannis S
YS
Varvaresou
Athanasia
A
Dracopoulou-Vabouli
Maria
M
Patsalis
Philippos C
PC
Shammas
Christos
C
Neocleous
Vassos
V
Phylactou
Leonidas A
LA
D000312:Adrenal Hyperplasia, Congenital / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D000483:Alleles; D003535:Cyprus; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D006115:Greece; D006801:Humans; D007010:Hyponatremia / Q000235:genetics; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase