RESUMEN
BACKGROUND: In humans, sex determination and differentiation is genetically controlled. Disorders of sex development (DSD) result in anomalies of the development of the external and internal genitalia. Variants in transcription factors such as SRY, NR5A1 and SOX9, can cause changes in gonadal development often associated with ambiguity of the external genitalia. OBJECTIVES: This study has been conducted to determine the frequency, types and associated genetic alterations in patients with DSD in the Algerian population. METHODS: Thirty patients were included. Based on their clinical presentation, thirteen patients presented with ambiguous external genitalia, thirteen patients presented with hypospadias and four patients presented with bilateral undescended testes. Karyotype analysis was performed on peripheral blood lymphocytes using standard R-banding. DNA was isolated from blood leukocytes for PCR reaction and mutational analysis of SRY and NR5A1 was done by direct sequencing. RESULTS: Most patients with ambiguous genitalia had a 46,XY karyotype. One patient had a deletion of SRY, otherwise no point mutations in SRY or NR5A1 genes were identified. However, a single NR5A1 polymorphism (p.Gly146Ala) in patient with 46,XX DSD has been detected. CONCLUSIONS: The absence of mutations in these genes suggests that there are others genes playing an important role in sex development and differentiation.