A Korean boy with 46,XX testicular disorder of sex development caused by<i>SOX9</i>duplication

Lee, Gyung Min; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won

doi:10.6065/apem.2014.19.2.108

Cited by 19 publications

(18 citation statements)

References 18 publications

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“…Sox9 is a direct target of SRY and has been shown to play a pivotal role in male sexual development. Ablation of Sox9 in humans [12,13] and mice [14][15][16] causes male-to-female phenotypic sex reversal while Sox9 gain-of-function, such as duplication of the SOX9 locus in humans [17,18] and Sryindependent upregulation of Sox9 in the fetal gonadal ridges of Wt1-Sox9 transgenic mice, causes testis formation in XX individuals [19]. The role of Sox9 in sex determination has mostly been studied in the context of two X chromosomes and focused on the period during fetal development when the sex determination takes place.…”

Section: Introductionmentioning

confidence: 99%

Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse1

Ortega

Ruthig

Ward

2015

Biology of Reproduction

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The Y chromosome gene Sry is responsible for sex determination in mammals and initiates a cascade of events that direct differentiation of bipotential genital ridges toward male-specific fate. Sox9 is an autosomal gene and a primary downstream target of SRY. The activation of Sox9 in the absence of Sry is sufficient for initiation of male-specific sex determination. Sry-to-Sox9 replacement has mostly been studied in the context of sex determination during early embryogenesis. Here, we tested whether Sry-to-Sox9 replacement affects male fertility in adulthood. We examined males with the Y chromosome carrying a deletion removing the endogenous Sry, with testes determination driven either by the Sox9 (XY(Tdym1)Sox9) or the Sry (XY(Tdym1)Sry) transgenes as well as wild-type males (XY). XY(Tdym1)Sox9 males had reduced testes size, altered testes shape and vasculature, and increased incidence of defects in seminiferous epithelium underlying the coelomic blood vessel region when compared to XY(Tdym1)Sry and XY. There were no differences between XY(Tdym1)Sry and XY(Tdym1)Sox9 males in respect to sperm number, motility, morphology, and ability to fertilize oocytes in vitro, but for some parameters, transgenic males were impaired when compared to XY. In fecundity trials, XY(Tdym1)Sry, XY(Tdym1)Sox9, and XY males yielded similar average numbers of pups and litters. Overall, our findings support that males lacking the testis determinant Sry can be fertile and reinforce the notion that Sry does not play a role in mature gonads. Although transgenic Sox9 overexpression in the absence of Sry results in certain testicular abnormalities, it does not translate into fertility impairment.

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Section: Introductionmentioning

confidence: 99%

Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse1

Ortega

Ruthig

Ward

2015

Biology of Reproduction

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“…As mentioned, Lee et al. () suggested that during paternal meiosis, 10% of the cases do not carry Y chromosome ( SRY negative). Interestingly, based on our study, the rate of the negative SRY in Iranian population was determined to be approximately 9.7%.…”

Section: Discussionmentioning

confidence: 95%

“…In most sex reversal cases, SRY is present ( SRY positive), while 10% of them do not carry this region on their X chromosome ( SRY negative). They show hypospadias, undescended testes or various degrees of inadequate virilisation in the external genitalia (Ergun‐Longmire et al., ; Lee, Ko, Shin, & Yang, ). The transcription of SOX9 (SRY‐box 9 gene) is enhanced in the genital ridge by SRY .…”

Section: Introductionmentioning

confidence: 99%

46,XX males: a case series based on clinical and genetics evaluation

et al. 2016

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46,XX male sex reversal syndrome is one of the rarest sex chromosomal aberrations. The presence of SRY gene on one of the X chromosomes is the most frequent cause of this syndrome. Based on Y chromosome profile, there are SRY-positive and SRY-negative forms. The purpose of our study was to report first case series of Iranian patients and describe the different clinical appearances based on their genetic component. From the 8,114 azoospermic and severe oligozoospermic patients referred to Royan institute, we diagnosed 57 cases as sex reversal patients. Based on the endocrinological history, we performed karyotyping, SRY and AZF microdeletion screening. Patients had a female karyotype. According to available hormonal reports of 37 patients, 16 cases had low levels of testosterone (43.2%). On the other hand, 15 males were SRY positive (90.2%), while they lacked the spermatogenic factors encoding genes on Yq. Commencing the testicular differentiation in males, the SRY gene is considered to be very important in this process. Due to homogeneous results of karyotyping and AZF deletion, there are both positive and negative SRY cases that show similar sex reversal phenotypes. Evidences show that there could be diverse phenotypic differences that could be raised from various reasons.

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“…The study suggested that the extra dose of SOX9 is sufficient to initiate testis differentiation in the absence of SRY ; however, the gonadal histology was not described. A recent case of a boy with normal genitalia has also been reported with a SOX9 duplication [Lee et al, 2014].…”

Section: Mechanisms Underlying Testis Differentiation In Sry -Negativmentioning

confidence: 99%

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects

Grinspon

Rey

2016

Sex Dev

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Virilisation of the XX foetus is the result of androgen excess, resulting most frequently from congenital adrenal hyperplasia in individuals with typical ovarian differentiation. In rare cases, 46,XX gonads may differentiate into testes, a condition known as 46,XX testicular disorders of sex development (DSD), or give rise to the coexistence of ovarian and testicular tissue, a condition known as 46,XX ovotesticular DSD. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue. Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed.

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A Korean boy with 46,XX testicular disorder of sex development caused bySOX9duplication

Cited by 19 publications

References 18 publications

Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse1

Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse1

46,XX males: a case series based on clinical and genetics evaluation

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects

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