Partial deletion of DMRT1 causes 46,XY ovotesticular disorder of sexual development

Abstract

Objective: Ovotesticular disorder of sexual development (DSD) is an unusual form of DSD, characterized by the coexistence of testicular and ovarian tissue in the same individual. In a subset of patients, ovotesticular DSD is caused by 46,XX/46,XY chimerism or mosaicism. To date, only a few monogenetic causes are known to be associated with XX and XY ovotesticular DSD. Design and methods: Clinical, hormonal, and histopathological data, and results of high-resolution array-comparative genomic hybridization (CGH) were obtained from a female patient with 46,XY ovotesticular DSD with testicular tissue on one side and an ovary harboring germ cells on the other. Results obtained by array-CGH were confirmed by RT-quantitative PCR. Results: We detected a deletion of ∼35 kb affecting exons 3 and 4 of the DMRT1 gene in a female patient with 46,XY ovotesticular DSD. To the best of our knowledge, this is the smallest deletion affecting DMRT1 presented to this point in time. Conclusions: We suggest that haploinsufficiency of DMRT1 is sufficient for both XY gonadal dysgenesis and XY ovotesticular DSD. Furthermore, array-CGH is a very useful tool in the molecular diagnosis of DSD. © 2012 European Society of Endocrinology.