IMPE Abstracts

Introduction: The 46, XY complete gonadal dysgenesis (CGD) is characterized by the presence of a female phenotype and completely undeveloped gonads (streak). This entity is considered as high-risk condition for the development of gonadal germ cell cancer.

Aim: to characterize the genetic etiology in a patient with 46, XY DSD and CGD.

Case report: A 12-year-old girl was admitted by a marked weight loss secondary to an abdominal tumor. Pathology report after surgery informed bilateral gonadal dysgerminoma with focal presence of gonadoblastoma suggesting a DSD condition. She presented a female phenotype with breast Tanner stage II at physical examination. Mullerian structure of 4.4 cm was found by US. No familiar history of DSD. Karyotype 46, XY Molecular studies and results: SRY gene could not be amplified in DNA extracted from peripheral blood lymphocytes (PBL) by PCR technique using two different pairs of primers. Chromosome studies were performed with G banding and FISH (SRY probe) in PBL culture. The karyotype was 46,XY .ish Yp11.3(SRY, SHGF-172115)x1[40]. In view of this discrepancy, we deepened the study with other techniques. SALSA MLPA P185-C2 (MRC-Holland) was performed for the analysis of copy number variation: a deletion of the Yp11.31 probe of the SRY gene was detected while the others specific probes for the X and Y chromosomes (GJB1_Xq13.1; PQBP1_Xp11.23; UTY_Yq 11.221; UTY_Yq 11.221_2) were present. Furthermore, the CGH-array showed a 4kb deletion in the Y chromosome arr[GRCh37]Yp11.31(2654908_2658865)x1. The SRY gene is the only gene involved in this region.

Discussion: Here we describe a girl with 46,XY DSD CGD due to a deletion in the short arm of Y chromosome that comprises SRY gene in whom the molecular diagnosis was challenging. The discrepancy in the result found with FISH technique could be explained to the fact that the probe used is 120 kb in size, much larger than the 4 kb deletion found; therefore it would allow hybridizing anyway, giving a false positive result. This study reinforces the importance of using different techniques for the genetic diagnosis in these complex cases. The risk for the development of gonadal germ cell cancer in this patient is might be related to the presence of a Y chromosome or at least sequences that retain the gonadoblastoma locus (GBY) located in Yp11 and Yq11.