Rare X;13 translocation with NR0B1 duplication in partial gonadal dysgenesis: A novel karyotype in DSD cases

Disorders of sex development (DSDs) are rare conditions characterized by discordance among chromosomal, gonadal, or anatomical sex. NR0B1 (DAX1) gene dosage is known to play a key role in sex determination.

We report a phenotypically female infant with ambiguous genitalia and a rare chromosomal aberration: 45,Y, der(X)t(13;X)(q10;p22.3),-13 mat. Clinical findings included clitoromegaly, penoscrotal hypospadias, a single perineal opening, and nonpalpable gonads. Cystourethroscopy and laparoscopy revealed internal Müllerian structures and testicular tissue on the left. Chromosomal microarray analysis identified a 2.2 Mb duplication at Xp21.2-p21.1 encompassing NR0B1, a dosage-sensitive gene involved in sex determination. Despite the presence of SRY and testicular tissue, NR0B1 duplication likely antagonized testicular development, resulting in partial gonadal dysgenesis. The patient's mother harbored the same structural aberration with NR0B1 triplication but exhibited a normal phenotype, suggesting sex-limited expression and potential skewed X-chromosome inactivation.

This case demonstrates how structural chromosomal rearrangements can alter NR0B1 gene dosage and disrupt sex development, even in the absence of coding sequence mutations. The findings emphasize the importance of comprehensive genetic and endocrine evaluation in DSDs and illustrate the variable expressivity of NR0B1 duplication depending on sex and X-inactivation patterns.