Testis formation in XX individuals resulting from novel pathogenic variants in Wilms’ tumor 1 ( WT1 ) gene
Copyright policy )Testis formation in XX individuals resulting from novel pathogenic variants in Wilms’ tumor 1 ( WT1 ) gene
Significance Sex development involves a precise spatiotemporal expression and interactions of numerous genetic factors, including the WT1 (Wilms tumor 1) gene. Complete and partial loss-of-function WT1 variants are associated with 46,XY disorders/differences of sex development (DSD). Some 46,XX individuals develop testis in absence of the testis-determining gene SRY . We describe a genotype/phenotype association where variants impacting the C-terminal zinc finger (ZF4) of WT1 cause testis development in 46,XX individuals. XX mice carrying a pathogenic variant of ZF4 display masculinization of the fetal gonads. Testis formation may be due to inappropriate interaction between the mutated WT1 and an essential ovarian determinant β-CATENIN. These data show that variants affecting a specific domain of a developmental transcription factor can switch organ fate.
- University of California, San Francisco United States
- New York University United States
- University of Pittsburgh Medical Center United States
- University of Szeged Hungary
- Touro University California United States
Male, Luteinizing hormone, 46, XX Testicular Disorders of Sex Development, Molecular Biology of Steroidogenesis and Disorders, sex determination, Temperature-Dependent Sex Determination, Gene, 46, Mice, Leydig cell, Endocrinology, Wilms' tumor, Zinc finger, Testis, https://purl.org/becyt/ford/3.2, Sex Determination and Differentiation in Organisms, beta Catenin, Cancer, ORGANOGENESIS, Sexual Differentiation, Prostate cancer, Life Sciences, Zinc Fingers, Gonad, Biological Sciences, XX TDSD/OTDSD, Sertoli cell, Sex reversal, WT1 Gene, Androgen receptor, 46,XX TDSD/OTDSD, Phenotype, Child, Preschool, Female, Disorders of sex development, Germline, organogenesis, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Testis determining factor, Biochemistry, Genetics and Molecular Biology, β-CATENIN, Genetics, Molecular Mechanisms of Kidney Development and Disease, Animals, Humans, https://purl.org/becyt/ford/3, WT1 Proteins, Spermatogenesis, Molecular Biology, Biology, Androgen insensitivity syndrome, SEX DETERMINATION, Y chromosome, Ovary, Infant, Β-CATENIN, Sex Determination, Hormone, WT1, Sexually Dimorphic Gene Expression, FOS: Biological sciences, Nuclear receptor, Mutation, Steroidogenic factor 1, Transcription factor
Male, Luteinizing hormone, 46, XX Testicular Disorders of Sex Development, Molecular Biology of Steroidogenesis and Disorders, sex determination, Temperature-Dependent Sex Determination, Gene, 46, Mice, Leydig cell, Endocrinology, Wilms' tumor, Zinc finger, Testis, https://purl.org/becyt/ford/3.2, Sex Determination and Differentiation in Organisms, beta Catenin, Cancer, ORGANOGENESIS, Sexual Differentiation, Prostate cancer, Life Sciences, Zinc Fingers, Gonad, Biological Sciences, XX TDSD/OTDSD, Sertoli cell, Sex reversal, WT1 Gene, Androgen receptor, 46,XX TDSD/OTDSD, Phenotype, Child, Preschool, Female, Disorders of sex development, Germline, organogenesis, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Testis determining factor, Biochemistry, Genetics and Molecular Biology, β-CATENIN, Genetics, Molecular Mechanisms of Kidney Development and Disease, Animals, Humans, https://purl.org/becyt/ford/3, WT1 Proteins, Spermatogenesis, Molecular Biology, Biology, Androgen insensitivity syndrome, SEX DETERMINATION, Y chromosome, Ovary, Infant, Β-CATENIN, Sex Determination, Hormone, WT1, Sexually Dimorphic Gene Expression, FOS: Biological sciences, Nuclear receptor, Mutation, Steroidogenic factor 1, Transcription factor
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