Abstract
Two sisters phenotypically normal females, presenting with tumor abdominal mass with histopathological findings of teratoma and gonadoblastoma associated to 46,XY male-to-female sex reversal syndrome, secondary to a duplication in DAX-1, possibly inherited of maternal gonadal mosaicism. Copy number variation and functional effects of the duplication were done by MLPA multiplex ligation-dependent probe amplification and real time PCR. DAX-1, also known as dosage sensitive sex reversal gene (DSS), is considered the most likely candidate gene involved in XY gonadal dysgenesis when overexpressed. The excess of DAX-1 gene disturbs testicular development by down regulation of SF-1, WT1, and SOX9. This is the first report of 46,XY sex reversal in two siblings who have a maternally inherited duplication of DAX-1 associated with reduced levels of expression of downstream genes as SOX9–SF1.
Highlights
Sex determination refers to the sexual characteristics of an organism, male or female, based on the chromosomal and genetic determinants
A genetic decontrol of genes such as SRY, SOX9, DAX-1, WNT4, WT1, DHH, and SF-1 can result in disorders of sex development (DSD), which refer to congenital conditions of atypical development of the chromosomal, gonadal or anatomical sex
We determined the duplication of DAX-1 by Multiplex ligation‐dependent probe amplification (MLPA) and validated the effects of it by mRNA expression levels in two 46,XY SRY-positive sisters with gonadal dysgenesis
Summary
Sex determination refers to the sexual characteristics of an organism, male or female, based on the chromosomal and genetic determinants. Sexual differentiation, is the physiologic and anatomic process that results in the development of a male or female phenotype. A genetic decontrol of genes such as SRY, SOX9, DAX-1, WNT4, WT1, DHH, and SF-1 can result in disorders of sex development (DSD), which refer to congenital conditions of atypical development of the chromosomal, gonadal or anatomical sex. During this stage, mutations, deletions or duplications in several of these genes have been identified, and affect the sexual differentiation and final phenotype of the individual. As in the case of gonadal dysgenesis in 46,XY individuals with DAX-1 duplication [4,5,6]
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