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2020, Number 1

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Rev Cub Gen 2020; 13 (1)

Identification of the I172N mutation of gene CYP21 in patients with congenital adrenal hyperplasia

Meunier CYR, González NJ, Reyes CD, López RI, Collazo MT

Language: Spanish
References: 27
Page: 1-13
PDF size: 592.64 Kb.


ABSTRACT

Introduction: Congenital adrenal hyperplasia comprises a number of autosomal recessive inheritance disorders caused by deficiency in any of the enzymes of the suprarenal steroidogenic pathway. Over 90% of the cases are due to a deficit in 21-hydroxylase activity resulting from mutations in the CYP21A2 gene. In 75% of the patients these mutations are microconversions originating in a nearby homologous pseudogene. One of the most common is the I172N mutation associated to severe forms of the disease.
Objective: Detect the I172N mutation in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency and estimate its allele frequency so as to determine the relevance of its incorporation into the scheme of molecular study of the disease.
Methods: Analysis was conducted of 79 DNA samples from non-consanguineous patients with a clinical diagnosis of the disease. The strategy applied consisted in specific amplification of the CYP21A2 gene followed by nested PCR-ACRS for amplification of locus I172N and eventual enzyme digestion.
Results: I172N mutation was detected in 8 cases: 3 homozygous and 5 heterozygous. Allele frequency was 0.0696. Four of the patients with I172N were compound heterozygous with other previously studied mutations. The results obtained by PCR-ACRS / enzyme digestion were verified by DNA sequencing in three cases, for the three possible genotypes.
Conclusions: Based on the high allele frequency obtained, it is considered indispensable to incorporate detection of the I172N mutation into the molecular study of patients with congenital adrenal hyperplasia due to 21-hydroxyase deficiency.


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