title: 46,XX testicular disorder of sexual development with SRY-negative caused by some unidentified mechanisms: a case report and review of the literature.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Tian-Fu
authors.initials: TF
authors.lastname: Li
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Wu
authors.forename: Cui
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Jiang
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Cui
authors.affiliation: Department of Reproduction and Genetics, Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China. xinyixia78@gmail.com.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Xia
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Shi
mesh_terms: D058531:46, XX Testicular Disorders of Sex Development / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D017353:Gene Deletion; D024282:Genes, sry / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D007265:Inhibins / Q000032:analysis; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D013737:Testis / Q000473:pathology; D014746:Vimentin / Q000032:analysis
chemical_list: D014746:Vimentin; D007265:Inhibins