Molecular genetic analysis of CYP21A2 gene in patients with congenital adrenal hyperplasia.
BACKGROUND
Congenital adrenal hyperplasia (CAH) is one of the inborn errors of metabolic disorder inherited in an autosomal recessive manner caused by the defects in the steroid 21 hydroxylase CYP21A2 gene. We analyzed the genotype of 62 patients with classic CAH.


OBJECTIVE
To find out the underlying mutations of CYP21A2 gene.


METHODS
Cohort of CAH patients.


METHODS
Sixty-two patients with CAH were recruited from the endocrine clinic at AIIMS. Electrochemiluminiscence method was used for estimating the levels of cortisol. Radioimmunoassay kit-based method was used for estimating the 17 OHP levels. Polymerase chain reaction amplification was done using specific primers to amply the CYP21A2 gene.


METHODS
Statistical analysis was done by using Epi Info Version 3.5.1.2008.


RESULTS
Out of 62 patients, 50 were simple virilizers (SV) and 12 were salt wasters (SW). Fifty-six were females and six were males. Five 46, XX children were reared as males. Age at presentation varied from 8 months to 38 years. Molecular genetic analysis revealed that the highest number of patients harboured (In 2) IVS2-13 A/C > G (48%), followed by p.P30L (46%), p.Q318X (35%), (D 8 bp) deletion 8 bp (26%), p.I172N (26%), and p. R356W (20%) mutations.


CONCLUSIONS
This is among the few studies to analyze the mutational spectrum of CYP21A2 gene in a large CAH cohort from India. Molecular diagnosis of CYP21A2 gene should be considered as part of the CAH evaluation to assess the risk of the patients/parents/siblings and to offer genetic counseling.
Department of Endocrinology and Metabolism, and Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Eunice
E
Marumudi
Arundhati
A
Sharma
Bindu
B
Kulshreshtha
Rajesh
R
Khadgawat
Madan L
ML
Khurana
Ariachery C
AC
Ammini