In mammals, a synchronization of molecular, cellular and hormonal events are necessary to determine a normal sexual development. In humans, abnormalities in these events can affect the normal gonadal and sexual development. These abnormalities cause the disorders of sexual development (DSD). The DSD patients present a wide phenotypic spectrum that can range from genital ambiguities, disorders of pubertal development to infertility. The cause of 46, XY DSD may be related to abnormalities of genes involved in male sexual differentiation, abnormalities in cellular hormone receptors or in production and action of testosterone and dihydrotestosterone. A considerable number of 46,XY DSD patients has not elucidated their disorder etiology. These patients are classified as indeterminate 46, XY DSD. The enzyme steroid 5alpha reductase 2 (5±RD2) catalyses the conversion of testosterone, secreted by the fetal testis, to dihydrotestosterone (DHT), which is required for the virilization of external genitalia. The 5±RD2 enzyme synthesis in the genital skin is extremely important to the normal differentiation of male external genitalia. In patients with 46, XY DDS due to 5±RD2 deficiency, the reduction of the testosterone in its active metabolite DHT not occur accurately, and its determines an undervirilization of the external genitalia in male fetus. The affected individuals have a large phenotypic spectrum that can range from ambiguous external genitalia, with microphallus and hypospadias to female external genitalia with isolated clitoromegaly. The aim of this study is research the presence of mutations in SRD5A2 gene in a group of 36 patients with indeterminate 46, XY DSD. In this study, the genomic DNA will be amplified by polymerase chain reaction (PCR) technique using specific primers to the SRD5A2 gene followed by the automatic sequencing of the products. Moreover, the multiplex ligation-dependent probe amplification (MLPA) technique will be used to search SRD5A2 gene deletions.
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