Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency

Year 2018, Volume: 35 Issue: 3, 63 - 69, 31.10.2019

Berk Özyılmaz , Murat Aydın , Gönül Oğur

Abstract

INTRODUCTION

Ambiguous genitalia is seen as the most
common phenotypic reflection of sexual development disorders. Congenital
adrenal hyperplasia (CAH) is the most common cause of ambiguous genitalia,
while the most common cause of CAH is a 21-hydroxylase deficiency with a rate
of 90-95%. The disease is caused by mutations in the CYP21A2 gene located at
6p21.3. It is inherited in an autosomal recessive manner. Seven previously
identified point mutations,  an 8-bp
deletion and large deletions, have significant role in the etiology of the
disease.

In this study, we aimed to report CYP21
molecular genetic evaluation by RFLP and MLPA methods in classic CAH patients
with 21-hydroxylase deficiency.

MATERIAL
AND METHODS

In this study, 26 patients with pre-diagnosis
of Classic Type Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
were reported. Seven previously identified point mutations, an 8-bp deletion,
and large deletions were analyzed by PCR-RFLP methods in the patient group.
For the MLPA study, SALSA MLPA KIT P050-B2
CAH (Lot0408) kit which was produced by MRC Holland was used.

RESULTS

In 21 (80%) of 26 patients analyzed, causative
mutations were found. The most frequent mutation was the large deletions (6
patients, 12 allels), accounting 23% of the patients.

CONCLUSION

In 21 (80.7%) of 26 patients, the causative
mutations were found by using PCR (8-bp del. and large deletions) and RFLP (7
known point mutations) methods. MLPA
analysis confirmed all of the deletions detected by PCR-RFLP, and the 83% of
the detectable point mutations with MLPA. A complete genotype-phenotype
relationship could be established in all patients in whom mutation could be
detected in the study group.

Keywords

CAH, RFLP, MLPA, Genotype-Phenotype

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