Investigation of cyp21a2 gene variants in iranian patients with congenital adrenal hyperplasia

Neda Asghari kollahi,1 Fahimeh baghbani-arani,2,* Azadeh shojaei,3

1. Department of Genetics & Biotechnology, School of Biological Science, Varamin-Pishva branch, Islamic Azad University, Va
2. Department of Genetics & biotechnology, School of Biological Science, Varamin-Pishva branch, Islamic Azad University, Va
3. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran,



Congenital adrenal hyperplasia (cah) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by cyp21a2 gene mutations. the aim of the study was to describe comprehensive cyp21a2 mutation analysis in the iranian population with cah.


Cyp21a2 mutation analysis was performed in 25 iranian patients. direct dna sequencing of whole cyp21a2 gene and polymerase chain reaction with sequence-specific primers for detection of cyp21a1p/cyp21a2 chimeras were combined.


Complex alleles comprising types three compound heterozygote mutations were identified; p.i172n/exon6 cluster (16%) , p.i172n/exon6 cluster, p.v281l (32%) and ivs2-13a>c,g/ exon6 cluster, p.v281l (4%). two different mutations in the heterozygous state; exon6 cluster (8%) and exon6 cluster/p.v281l (4%) and p.g110efs the 8 nucleotide (nt) deletion in exon 3 (4%), i172n in the heterozygote state (12%) . a very high frequency of variants was found in cyp21a2, including: rs6477(56%), rs6468(8%), rs6474(12%), rs6472(16%), rs6473(16%), rs6446(16%) and rs193922546, rs530758070, rs11970671, rs61732108, rs778403992, rs1058152 and rs562025438 each (4%) either and also more importantly a new heterozygote variant c.29-31delctg (rs61338903) has also been found


The distribution of cyp21a2 mutations was analyzed among cah patients. the present study has shown for the first time, a very high frequency of variants in cyp21a2 in iran. in addition, three pathogenic rare compound heterozygosity reported here may consider in genetic counseling of iranian ethnic group, also when the 21-hydroxylase deficiency clinically diagnosed by physicians.


21-hydroxylase deficiency• cyp21a1p/cyp21a2 chimeras • cah • compound heterozygote • cyp21a2