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46,XX Testicular Disorder of Sexual Development With SRY-negative Caused by Some Unidentified Mechanisms: A Case Report and Review of the Literature

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Review

46,XX Testicular Disorder of Sexual Development With SRY-negative Caused by Some Unidentified Mechanisms: A Case Report and Review of the Literature

Tian-Fu Li et al. BMC Urol.

Abstract

Background: 46,XX testicular disorder of sex development is a rare genetic syndrome, characterized by a complete or partial mismatch between genetic sex and phenotypic sex, which results in infertility because of the absence of the azoospermia factor region in the long arm of Y chromosome.

Case presentation: We report a case of a 14-year-old male with microorchidism and mild bilateral gynecomastia who referred to our hospital because of abnormal gender characteristics. The patient was treated for congenital scrotal type hypospadias at the age of 4 years. Semen analysis indicated azoospermia by centrifugation of ejaculate. Levels of follicle-stimulating hormone and luteinizing hormone were elevated, while that of testosterone was low and those of estradiol and prolactin were normal. The results of gonadal biopsy showed hyalinization of the seminiferous tubules, but there was no evidence of spermatogenic cells. Karyotype analysis of the patient confirmed 46,XX karyotype and fluorescent in situ hybridization analysis of the sex-determining region Y (SRY) gene was negative. Molecular analysis revealed that the SRY gene and the AZFa, AZFb and AZFc regions were absent. No mutation was detected in the coding region and exon/intron boundaries of the RSPO1, DAX1, SOX9, SOX3, SOX10, ROCK1, and DMRT genes, and no copy number variation in the whole genome sequence was found.

Conclusion: This study adds a new case of SRY-negative 46,XX testicular disorder of sex development and further verifies the view that the absence of major regions from the Y chromosome leads to an incomplete masculine phenotype, abnormal hormone levels and infertility. To date, the mechanisms for induction of testicular tissue in 46,XX SRY-negative patients remain unknown, although other genetic or environmental factors play a significant role in the regulation of sex determination and differentiation.

Figures

Figure 1
Figure 1
Histological examination of gonadal tissue by HE staining under light microscopy. The results of gonadal biopsy showed the appearance of hyalinization of the seminiferous tubules, but without evidence of spermatogenic cells. (A) and (B) are testis tissue; (C) and (D) are epididymis tissue. The black arrows show hyalinization of seminiferous tubules in (A) and (B).
Figure 2
Figure 2
Immunohistochemical staining of inhibin and vimentin was observed by light microscopy. Immunohistochemical analysis also confirmed the gonadal tissue had positive immunoreactivity to inhibin (A) and vimentin (B), which indicated the presence of Leydig cells. The black arrows in (A) indicated that the tissue was positive for inhibin by immunohistochemical staining.
Figure 3
Figure 3
FISH was used to analysis of metaphase chromosomes of a second case using the LSI SRY (orange) / CEP X (green) probes. FISH showed the absence of the SRY gene in our patient, while there were two green signals of the X chromosome (white arrows).
Figure 4
Figure 4
Result of multiplex polymerase chain reaction (PCR). Multiplex 1: ZFX/ZFY (690 bp), sY84 (320 bp), and sY127 (274 bp); Multiplex 2: SRY (472 bp) and sY86 (326 bp); Multiplex 3: sY254 (400 bp), sY134 (301 bp), and sY255 (126 bp). M: DL1000 DNA Marker; W: a DNA sample from a woman as a negative control; N: a DNA sample from a normal fertile man as a positive control; P: a DNA sample from the patient; B: a blank (water) control.
Figure 5
Figure 5
Affymetrix Cytogenetics Whole Genome 2.7 M Arrays were employed to detect genomic DNA. No change in the ratio was observed, which indicated no variation in copy number between positions 64000 kb and 72000 kb of chromosome 17q24.2-25.1.

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Pre-publication history
    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2490/14/104/prepub

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