WT1: A single gene associated with multiple and severe phenotypes

Ferrari, Maria Tereza Martins; Elias, Felipe Martins; Gomes, Nathalia Lisboa Rosa Almeida; Batista, Rafael Loch; Faria, José Antonio Diniz; Nishi, Mirian Yumie; Mendonca, Berenice Bilharinho de; Domenice, Sorahia

doi:10.1016/j.endmts.2023.100143

Cited by 2 publications

(1 citation statement)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pathogenic WT1 variants are associated with several phenotypes, including 46,XY and 46,XX DSD ( 135 ).…”

Section: Sry -Negative With Pathogenic Mechanisms Not Comple...mentioning

confidence: 99%

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Ferrari,

Silva,

Nishi

et al. 2024

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of SRY to the X chromosome or an autosome. In the absence of SRY, other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.

show abstract

“…Pathogenic WT1 variants are associated with several phenotypes, including 46,XY and 46,XX DSD ( 135 ).…”

Section: Sry -Negative With Pathogenic Mechanisms Not Comple...mentioning

confidence: 99%

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Ferrari,

Silva,

Nishi

et al. 2024

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

show abstract

Genetic diagnosis in XY disorders of sex development

Priyadarshini,

Sharma,

Jain

2024

JPED

View full text Add to dashboard Cite

XY disorders of sex development (XY DSD) comprise a class of heterogeneous genetic entities that result in discrepancies between chromosomal, gonadal, and phenotypic sex due to a reduction in androgen synthesis or action. The chief categories of disorders include gonadal dysgenesis, disorders with reduced androgen production (biosynthetic defect – either alone or in conjunction with impaired glucocorticoid and/or mineralocorticoid synthesis), and insensitivity to androgen action. While conventional diagnostic modalities, encompassing karyotyping, biochemistry, radiology, and, in a few cases, diagnostic laparoscopy, help in formulating a provisional diagnosis, molecular genetic testing is key to arriving at a precise etiology. Besides ending the diagnostic uncertainty, a molecular diagnosis helps to predict the natural course in terms of pubertal development and potential for fertility, thus contributing to decisions on the gender of rearing; and guides on surveillance for extragenital features and the risk of recurrence in subsequent pregnancies. This paper broadly discusses the genetic basis of XY DSD, different modalities of genetic testing, and their utility and limitations.

show abstract

WT1: A single gene associated with multiple and severe phenotypes

Cited by 2 publications

References 70 publications

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Genetic diagnosis in XY disorders of sex development

Contact Info

Product

Resources

About