A SOX9 duplication and familial 46,XX developmental testicular disorder.

  title={A SOX9 duplication and familial 46,XX developmental testicular disorder.},
  author={James J. Cox and Lionel R Willatt and Tessa Homfray and Christopher Geoffrey Woods},
  journal={The New England journal of medicine},
  volume={364 1},
To the Editor: Female-to-male sex reversal in humans is rare, and when it is familial, it is extremely rare. We describe a family with a 46,XX testicular disorder of sex development in which three adult males (two brothers and a paternal uncle) were determined to be female according to karyotype (46,XX) and were negative for the SRY gene (Figure 1). The secondary sexual characteristics, behavior, growth and development, and skeletal development in these men were all normal male. Their general… 

Figures from this paper

Three cases of rare SRY-negative 46,XX testicular disorder of sexual development with complete masculinization and a review of the literature

Three cases of rare SRY-negative 46,XX testicular disorder of sexual development with complete masculinization and a review of the literature show that sex differentiation related genes such as SOX9, FGF9, DAX1, WT1, RSPO1, and SOX10, which are located on either autosomes or the X chromosome, may have a role in gonad development and function.

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

Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

Similar Cause, Different Phenotype: SOX9 Enhancer Duplication in a Family

The data support the phenotypic modularity impact – incomplete penetrance and variable expressivity – of very similar but non-identical CNVs, which are possibly inherited across three generations and could alternatively modify the inner structure and functioning of SOX9’stopologically associated domain (TAD) due to the differing fine TAD arrangements.

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

Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed.

A Rare Case of Testicular Disorder of Sex Development in a Dog (78,XX; SRY-Negative) with Male External Genitalia and Detection of Copy Number Variation in the Region Upstream of the SOX9 Gene

Observations are in agreement with earlier suggestions that a high number of copies at the CNVR upstream of SOX9 may be associated with this type of DSD.

46,XX Male Disorder of Sexual Development: A Case Report

An adolescent who presented with low testicular volume and who was diagnosed as a 46,XX male was reported, and SRY positivity was demonstrated in the patient by fluorescence in situ hybridization method.

Testicular XX (SRY-Negative) Disorder of Sex Development in Cat

The first case of an XX (SRY-negative) DSD cat, which possesses a tortoiseshell coat associated with male-like external genitalia, and cytogenetic and genetic analyses showed a female karyotype associated with the absence of the SRY gene is described.

Duplication of SOX9 is not a common cause of 46,XX testicular or 46,XX ovotesticular DSD

It is found that duplication in the region of 17q that contains SOX9 is not a common cause of testis development in subjects with SRY-negative 46,XX testicular or ovotesticular DSD.

Sox9 Duplications Are a Relevant Cause of Sry-Negative XX Sex Reversal Dogs

This work provides for the first time a causative mutation for the XXSR condition in the dog, and supports the idea that the dog represents a good animal model for the study ofXXSR condition caused by abnormalities in the SOX9 locus.

SRY-negative in 46, XX Male Testicular DSD: a case report

A comprehensive management including clinical, cytogenetic and molecular analyses have indicated that undiscovered genetic or environmental factors needs to be elucidated for precise diagnosis of DSD in a boy with ambiguous genitalia.



Sox9 induces testis development in XX transgenic mice

It is shown that Sox9 is sufficient to induce testis formation in mice, indicating that it can substitute for the sex-determining gene Sry, which is associated with male-to-female sex reversal in humans.

Long-range activation of Sox9 in Odd Sex (Ods) mice.

It is demonstrated that in Ods, the Dct promoter is capable of acting over a distance of 1 Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium of the eye, causing the observed microphthalmia.

Long-range regulation at the SOX9 locus in development and disease

How the identification of novel lesions surrounding SOX9 support the existence of tissue specific enhancers acting over a large distance to regulate expression of the gene during craniofacial development is discussed, and the potential for discovery of additional regulatory elements within the extendedSOX9 control region is highlighted.

Genetic mechanisms underlying male sex determination in mammals

  • R. Piprek
  • Biology
    Journal of Applied Genetics
  • 2010
In the absence of Sry, the predomination of the female pathway results in the realization of a robust genetic program that drives ovarian differentiation.

Imerslund‐Gräsbeck Anemia

A follow‐up study has been performed on 14 patients, now aged 6–46 years, with Imerslund‐Gräsbeck anemia, with moderate signs of chronic glomerulopathy of mesangioproliferative type in both patients.

Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo.

Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin.

Receptor-mediated endocytosis in renal proximal tubule

The endocytic apparatus is highly developed in the proximal tubule demonstrating the high capacity of the cells; however, under certain circumstances like diseases affecting the glomeruli, the system is overloaded resulting in proteinuria.