Duplication of dosage sensitive sex reversal area in a 46, XY patient with normal sex determining region of Y causing complete sex reversal

Anil, Sukumaran; Desmangles, Jean-Claude; Gartner, Lou Ann; Buchlis, John

doi:10.1515/jpem-2012-0354

Cited by 19 publications

(16 citation statements)

References 19 publications

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“…Consistent with SOX9 , the DAX1 gene might also function downstream of the SRY gene in the sex-determination pathway. Overexpression of the DAX1 gene could cause female-to-male sex reversal [ 24 ]. ROCK1 (Rho-associated, coiled-coil protein kinase 1) phosphorylates and activates SOX9 in Sertoli cells to initiate testes formation [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

46,XX testicular disorder of sexual development with SRY-negative caused by some unidentified mechanisms: a case report and review of the literature

Zhang

et al. 2014

BMC Urol

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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.

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Section: Discussionmentioning

confidence: 99%

46,XX testicular disorder of sexual development with SRY-negative caused by some unidentified mechanisms: a case report and review of the literature

Zhang

et al. 2014

BMC Urol

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“…In addition, the AMH pattern of expression is related to SF1 and WT1 , which are also modulated by DAX1 [Ledig et al, 2010]. Overexpression of DAX1 also represses INSL3 and testosterone in Leydig cells which are involved in testis descent, Wolffian stabilization and external genital virilization [Sanlaville et al, 2004;Zarate et al, 2011;Sukumaran et al, 2013]. Our patient has well-developed Müllerian ducts, but no evidence of gonads (even atrophic), Wolffian derivatives and external genital virilization.…”

Section: Discussionmentioning

confidence: 65%

“…Intellectual disability and autism spectrum phenotypes, such as Asperger syndrome, have been reported in patients with mutation in the NLGN4X gene (OMIM 300427) and IL1RAPL1 (OMIM 300143). The GK gene is responsible for glycerol kinase deficiency, and the DMD gene is related to Duchenne muscular dystrophy [Sukumaran et al, 2013]. Mutations in MID1 (OMIM 300552), OFD1 (OMIM 300170), RPS6KA3 (OMIM 300075), ARX (OMIM 300382), KAL1 (OMIM 300836), OFD1 (OMIM 300170), and PDK3 (OMIM 300905) are associated to syndromes such as Opitz, Oral-facial-digital, CoffinLowry and Proud, Kallmann syndrome and Charcot-Marie-Tooth disease.…”

Section: Discussionmentioning

confidence: 99%

A Cytogenomic Approach in a Case of Syndromic XY Gonadal Dysgenesis

Simioni¹,

Monlleó

Queiroz

et al. 2016

Sex Dev

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This is the first molecular characterization of a female XY patient with an Xp duplication due to an X;22 translocation. Array CGH detected a copy number gain of ∼36 Mb in the Xp22.33p21.1 region involving 150 genes. Clinical and molecular studies described in the literature have suggested DAX1 duplication as the major cause responsible for a sex reversal phenotype. Additionally, the interaction between genes and their possible role in clinical features are presented to support the discussion on genotype-phenotype correlation in cases of syndromic XY gonadal dysgenesis.

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“…The results of array showed that SRY gene was also present in the duplication region and normal copies region, and the deletion region did not contain the SRY gene. Duplication or haploinsufficiency, such as DAX1, WNT4 or SOX9, SF1, WT1, and DMRT1‐DMRT2, has been considered responsible for the development of 46,XY sex reversal, and therefore, the duplication of SRY gene in our patient may play a significant role in the etiology of the disease in this case.…”

Section: Discussionmentioning

confidence: 86%

Duplication of dosage sensitive sex reversal area in a 46, XY patient with normal sex determining region of Y causing complete sex reversal

Cited by 19 publications

References 19 publications

46,XX testicular disorder of sexual development with SRY-negative caused by some unidentified mechanisms: a case report and review of the literature

46,XX testicular disorder of sexual development with SRY-negative caused by some unidentified mechanisms: a case report and review of the literature

A Cytogenomic Approach in a Case of Syndromic XY Gonadal Dysgenesis

A de novo derivative Y chromosome (partial Yq deletion and partial duplication of Yp and Yq) in a female with disorders of sex development

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