Mutation Analysis of theCYP21A2Gene in the Iranian Population

Abstract

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.

In silico structural, functional and pathogenicity evaluation of a novel mutation: An overview of HSD3B2 gene mutations

“…A few molecular studies have been published about CAH patients in Iran, and all of them have worked on CYP21A2 gene mutations (Vakili et al, 2005;Ramazani et al, 2008;Rabbani et al, 2011a). In this study, a homozygous coding mutation is reported in a 20 day old pseudohermaphrodite male due to substitution of G to C of codon 82 (at position 244), encompassing the membrane binding domain of 3βHSD enzyme.…”

“…Males would present hypospadias, and ambiguous genitalia; females would show normal or mild virilized external genitalia because this deficiency lowers the testosterone concentration for development of external genitalia (Pang, 1998). Molecular analysis of Iranian CAH patients has been carried out for CYP21A2 gene (Vakili et al, 2005;Ramazani et al, 2008;Rabbani et al, 2011aRabbani et al, , 2011b which accounts for more than 95% of the CAH defects in Iran. However, the remaining causal defects of CAH are unknown among this population.…”

Genotype–phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency

“…First, we analyzed a heterogeneous population as opposed to past reports, which were drawn from specific countries (18)(19)(20). Second, our data provide a framework for physicians to ascertain the prevalent form of CAH for a given genotype.…”

A CYP21A2 gene mutation in patients with congenital adrenal hyperplasia

“… 4 Recent studies showed that an IVS2 AS -13 (A/C to G) mutation is prevalent in the Iranians while p.Q319X is common in Turkey, Tunisia, and East India. 4 - 7 Different mutations result in variable deficiency of cortisol and aldosterone together with increased synthesis of androgen. 8 - 10 The genotype/phenotype correlation of CAH has been reported in different populations and ethnic groups.…”

“… 8 - 10 The genotype/phenotype correlation of CAH has been reported in different populations and ethnic groups. 4 - 7 Although the clinical presentations of CAH have been studied in Saudi children, literature review revealed no molecular report of 21-hydroxylase. 3 Therefore, the aim of this study was to determine the pattern of CYP21A2 gene-mutations in Saudi children with CAH, and to describe the clinical phenotype of these patients.…”