ESPE Abstracts

Introduction: Phenotype gender is the outcome of a long and coordinated set of fetal events that are controlled by genetic factors, hormonal factors and environmental factor. In the case of the 46XY fetus, SRY gene on chromosome Y determines the gender and cause bipotential gonad change to testes. And other factors such as sertolli cell by secreting anti-Mullerian hormone which leads to regression of the structures rooted in the paramesonephric ducts (tubes, womb, and vagina) and leydig cell that are found within the testicle tissues generate fetal testosterone that converts mesonephric ducts into the penetrating duct, seminal vesicles, and epididymis. Three common reasons that lead to the formation of female phenotype in an individual with 46XY karyotype are complete androgenic insensitivity syndrome (CAIS), Congenital adrenal hyperplasia (CAH), and complete dysgenesis of sexual glands. Here, we report two sisters with 46, XY DSD harboring a new mutation in the AR gene.

Case presentation: A 10 years old girl with female external genital organs (clitoris, major and minor labia, distinct vaginal and urethra orifices) was referred to the health clinic complaining about urine infection symptoms. Complete urine analysis and culture showed no urine infection. For further examination, abdominopelvic sonography was performed and showed that the womb and ovaries were not in their anatomical position. Two hypoechoic oval-shaped regions were observed in the right and left inguinal channels with dimensions of 26 × 10 × 9 mm and 24 × 4 × 8 mm. Both regions appeared as testicles. Magnetic resonance imaging was the same. Cytogenetic tests indicated that the patient was genetically male with a 46XY chromosome structure. After that her 5 years old sister was examined and was exactly the same. Sanger sequencing showed a novel hemizygous variant (c.2484T>A; p. phe828Leu) in AR (NM_000044.4) gene. They inherited this variant from their heterozygous mother. Their father did not harbor this variation.

Conclusion: Up to now, more than 497 mutation s in the AR gene have been registered in the HGMD database. In this study, a novel pathogenic variant in AR gene has been introduced. This finding helps in the genotype-phenotype correlation of AIS patients with this variation.