Mutation analysis of the CYP21A2 gene in the Iranian population.
BACKGROUND
Defects in the CYP21A2 gene cause steroid 21-hydroxylase deficiency, which is the most frequent cause of congenital adrenal hyperplasia. Forty four affected families were investigated to identify the mutation spectrum of the CYP21A2 gene.


METHODS
Families were subjected to clinical, biochemical, and molecular analyses. Allele-specific polymerase chain reaction amplification was used for eight common mutations followed by dosage analysis to exclude CYP21A2 deletions.


RESULTS
The most frequent mutations detected were gene deletions and chimera (31.8%). Other mutation frequencies were as follows: Q318X, 15.9%; I2G, 14.8%; I172N, 5.8%; gene duplication, 5.7%; R356W, 8%; and E6 cluster mutations, 2.3%. Direct sequencing of the CYP21A2 gene revealed R316X, P453S, c.484insT, and a change at the start codon. Different modules carried by patients were classified into five different haplotypes. The genotype phenotype correlation (positive predictive value) for group null, A, B, and C were 92.3%, 85.7%, 100%, and 0, respectively.


CONCLUSIONS
Methods used will be helpful for carrier detection and antenatal diagnosis, especially with inclusion of the multiplex ligation probe dependent amplification technique, which is easier for routine tests in comparison with other methods. Mutation frequencies indicate that Iranians are possible descendants of Asians and Europeans.
Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Bahareh
B
Rabbani
Nejat
N
Mahdieh
Mohammad Tahgi Haghi
MT
Ashtiani
Bagher
B
Larijani
Mohammad Taghi
MT
Akbari
Maria
M
New
Alan
A
Parsa
Jan P
JP
Schouten
Ali
A
Rabbani
D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007492:Iran; D008297:Male; D009154:Mutation; D059645:Mutation Rate; D011237:Predictive Value of Tests; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase