46,XX ovotesticular DSD associated with a SOX3

GRINSPON R. P; NEVADO J; MORI ALVAREZ M; DEL REY G; DR ROBERTO CASTERA; VENARA M; CHIESA A; DR MIGUEL L PODESTA; LAPUNZINA P; REY RA

CLINICAL ENDOCRINOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

0300-0664

Background: Ovotesticular DSD is arare disorder defined by the presence of both ovarian and testicular tissues inthe same individual. SRY is presentin approximately 1/3 of patients with 46,XX ovotesticular DSD. In SRY-negative ovotesticular DSD, themechanism responsible for the presence of testicular tissue is not yetunderstood. Case presentation: A malepatient was referred to us for hypospadias and bilateral cryptorchidism at 2.5years of age. He had a trophic phallus (32 mm x 13 mm) with coronal hypospadiasand hypoplastic scrotum. Right gonad was palpable in the inguinal region; nogonad was palpable on the left side. Basal AMH (216 pmol/L) and hCG-stimulatedtestosterone (30 ng/dl) were low, indicating that dysgenetic testicular tissuewas present. Gonadotrophins were not elevated, with FSH predominance (LH<0.10 U/L, FSH 0.73 U/L). Karyotype was 46,XX. These results were suggestiveof the presence of ovarian tissue. Diagnostic laparoscopy was performed, andthe histopathological study confirmed the presence of bilateral ovotestes.Absence of SRYin peripheral leukocyteswas documented by QF PCR analysis (Devyser Kit). A genome-wide copynumber analysis, performed by single-nucleotide polymorphism using CytoSNP-850Kmicroarray (Illumina), confirmed the absence of SRY and of Y chromosome sequences. Furthermore, a de novo duplication of 502,127 bp atXq27.1 chromosomal region encompassingSOX3 gene was evidenced. Metaphase FISH analysis using a BAC probehybridizing on both X homologues demonstrated a tandem duplication of thisregion.Conclusion and Discussion: This is the first case of SRY-negative 46,XXOvotesticular DSD in whom a genetic association (SOX3 duplication) is reported. These results are in line withevidence in mice indicating that, inthe absence of SRY, gain-of-functionof SOX3 induces testisdifferentiation in the XX bipotential gonad. SOX3, as a surrogate of SRY, wouldact synergistically with SF1 to upregulate SOX9 expression and stimulatetesticular organogenesis.