Department of Sciences for Health Promotion and Mother and Child Care G. DAlessandro, University of Palermo, Palermo, Italy. piccionemaria@libero.it; salzanoemanuela@gmail.com
Denys-Drash is a rare genetic disorder related to mutations in WT1 gene and characterized by the triad of 46,XY disorder of sex developmental, renal dysfunction and Wilms Tumor. To date about 150 patients with Denys-Drash Syndrome have been reported
Denys-Drash syndrome
194080Frasier syndrome136680Meacham syndrome608978Mesothelioma, somatic156240Nephrotic syndrome, type 4256370Wilms tumor, type 1194070AliasWilms Tumor 1NPHS4Last Three Zinc Fingers Of The DNA-Binding Domain Of WT1Amino-Terminal Domain Of EWSWilms Tumor ProteinEWS-WT1WIT-2AWT1WAGRGUDNoteWT1 gene encodes for a DNA-binding protein including four zinc-finger motifs at the C-terminus and a proline\/glutamine-rich DNA-binding domain at the N-terminus. It acts as trascriptional modulator that has an essential role in the normal development of the urogenital system. This gene has a biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues.Dna description10 exons, extending for 48 kb of genomic DNA.TranscriptionAlternative splicing at two sites results in four major different zinc finger protein isoforms (molecular weights of between 52 and 54 kDa).DescriptionAlternative splicing at the two sites generates 4 major different isoforms, respectively either including or excluding exon 5 and including or excluding three amino-acids - lysine, threonine and serine (KTS positive or negative isoforms). The KTS isoforms are highly conserved throughout evolution, indicating a very biological important function.ExpressionKidney, ovary, testis, liver, heart and hematopoietic cells.LocalisationMainly nuclear, depending on the different isoforms.FunctionWT1 mediates trascriptional activation and\/or repression of several gene targets. It particular seems to directly synergize with SF1 participating to steroidogenesis and in sexual differentiation by regulating expression of the polypeptide hormone mullerian inhibiting substance. In addition WT1 plays a key role in podocyte gene-expression and subsequently in podocyte differentiation (Nachtigat et al 1998; Lefebvre et al. 2015).NoteDenys-Drash WT1 mutations are clustered particularly in the exons encoding Zf2 and Zf3in and behave as dominant negatives. Most WT1 mutations in rasier patients affect the exon 9 donor splice site resulting in a functional imbalance of WT1 +KTS isoforms, as detected on dysgenetic gonads by RTPCR (Klam et al.1998; Haber et al.1991). In addition transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) seems to have a more restrictive podocyte set of genes whose expression depends on these alternatively spliced isoforms (Klamt et al 1998; Lefebvre et al. 2015). To be noted Registryhttp:\/\/www.uke.de\/kliniken-institute\/kliniken\/kinder-und-jugendmedizin\/ Registry for Patients with WT1 Mutation Associated Diseases - UKE - Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Kinder- und Jugendmedizinhttps:\/\/www.amc.nl\/web\/Het-AMC\/Afdelingen\/Overzicht\/Klinische-Informatiekunde-KIK\/Klinische-Informatiekunde-KIK\/Department.htm ESPN\/ERA-EDTA Registry: European Registry for Children on Renal Replacement Therapy AMC - Academisch Medisch Centrum- Afdeling Klinische InformatiekundeDatabaseshttp:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=WT1 Gene WT1 (GeneCards)http:\/\/ghr.nlm.nih.gov\/condition\/denys-drash-syndrome Denys-Drash syndrome (Genetic Home Reference)BibliographyPubmed IDLast YearTitleAuthors219113222011Current concepts in disorders of sexual development.Öçal G et al182031542008Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.Antonius T et al93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al21725001990Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).Jadresic L et al94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al259933182015Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.Lefebvre J et al95901781998Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.Nachtigal MW et al169271062006WT1 and glomerular diseases.Niaudet P et al13275251992Inherited WT1 mutation in Denys-Drash syndrome.Coppes MJ et al16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al107622962000Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?Koziell A et al80719741994The Denys-Drash syndrome.Mueller RF et al External Links GARDERN GENTURISOMIMORPHANETMeSH Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Aditional Info × Loading, wait...
Frasier syndrome
136680Meacham syndrome608978Mesothelioma, somatic156240Nephrotic syndrome, type 4256370Wilms tumor, type 1194070AliasWilms Tumor 1NPHS4Last Three Zinc Fingers Of The DNA-Binding Domain Of WT1Amino-Terminal Domain Of EWSWilms Tumor ProteinEWS-WT1WIT-2AWT1WAGRGUDNoteWT1 gene encodes for a DNA-binding protein including four zinc-finger motifs at the C-terminus and a proline\/glutamine-rich DNA-binding domain at the N-terminus. It acts as trascriptional modulator that has an essential role in the normal development of the urogenital system. This gene has a biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues.Dna description10 exons, extending for 48 kb of genomic DNA.TranscriptionAlternative splicing at two sites results in four major different zinc finger protein isoforms (molecular weights of between 52 and 54 kDa).DescriptionAlternative splicing at the two sites generates 4 major different isoforms, respectively either including or excluding exon 5 and including or excluding three amino-acids - lysine, threonine and serine (KTS positive or negative isoforms). The KTS isoforms are highly conserved throughout evolution, indicating a very biological important function.ExpressionKidney, ovary, testis, liver, heart and hematopoietic cells.LocalisationMainly nuclear, depending on the different isoforms.FunctionWT1 mediates trascriptional activation and\/or repression of several gene targets. It particular seems to directly synergize with SF1 participating to steroidogenesis and in sexual differentiation by regulating expression of the polypeptide hormone mullerian inhibiting substance. In addition WT1 plays a key role in podocyte gene-expression and subsequently in podocyte differentiation (Nachtigat et al 1998; Lefebvre et al. 2015).NoteDenys-Drash WT1 mutations are clustered particularly in the exons encoding Zf2 and Zf3in and behave as dominant negatives. Most WT1 mutations in rasier patients affect the exon 9 donor splice site resulting in a functional imbalance of WT1 +KTS isoforms, as detected on dysgenetic gonads by RTPCR (Klam et al.1998; Haber et al.1991). In addition transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) seems to have a more restrictive podocyte set of genes whose expression depends on these alternatively spliced isoforms (Klamt et al 1998; Lefebvre et al. 2015). To be noted Registryhttp:\/\/www.uke.de\/kliniken-institute\/kliniken\/kinder-und-jugendmedizin\/ Registry for Patients with WT1 Mutation Associated Diseases - UKE - Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Kinder- und Jugendmedizinhttps:\/\/www.amc.nl\/web\/Het-AMC\/Afdelingen\/Overzicht\/Klinische-Informatiekunde-KIK\/Klinische-Informatiekunde-KIK\/Department.htm ESPN\/ERA-EDTA Registry: European Registry for Children on Renal Replacement Therapy AMC - Academisch Medisch Centrum- Afdeling Klinische InformatiekundeDatabaseshttp:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=WT1 Gene WT1 (GeneCards)http:\/\/ghr.nlm.nih.gov\/condition\/denys-drash-syndrome Denys-Drash syndrome (Genetic Home Reference)BibliographyPubmed IDLast YearTitleAuthors219113222011Current concepts in disorders of sexual development.Öçal G et al182031542008Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.Antonius T et al93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al21725001990Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).Jadresic L et al94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al259933182015Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.Lefebvre J et al95901781998Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.Nachtigal MW et al169271062006WT1 and glomerular diseases.Niaudet P et al13275251992Inherited WT1 mutation in Denys-Drash syndrome.Coppes MJ et al16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al107622962000Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?Koziell A et al80719741994The Denys-Drash syndrome.Mueller RF et al External Links GARDERN GENTURISOMIMORPHANETMeSH Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Aditional Info × Loading, wait...
Meacham syndrome
608978Mesothelioma, somatic156240Nephrotic syndrome, type 4256370Wilms tumor, type 1194070AliasWilms Tumor 1NPHS4Last Three Zinc Fingers Of The DNA-Binding Domain Of WT1Amino-Terminal Domain Of EWSWilms Tumor ProteinEWS-WT1WIT-2AWT1WAGRGUDNoteWT1 gene encodes for a DNA-binding protein including four zinc-finger motifs at the C-terminus and a proline\/glutamine-rich DNA-binding domain at the N-terminus. It acts as trascriptional modulator that has an essential role in the normal development of the urogenital system. This gene has a biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues.Dna description10 exons, extending for 48 kb of genomic DNA.TranscriptionAlternative splicing at two sites results in four major different zinc finger protein isoforms (molecular weights of between 52 and 54 kDa).DescriptionAlternative splicing at the two sites generates 4 major different isoforms, respectively either including or excluding exon 5 and including or excluding three amino-acids - lysine, threonine and serine (KTS positive or negative isoforms). The KTS isoforms are highly conserved throughout evolution, indicating a very biological important function.ExpressionKidney, ovary, testis, liver, heart and hematopoietic cells.LocalisationMainly nuclear, depending on the different isoforms.FunctionWT1 mediates trascriptional activation and\/or repression of several gene targets. It particular seems to directly synergize with SF1 participating to steroidogenesis and in sexual differentiation by regulating expression of the polypeptide hormone mullerian inhibiting substance. In addition WT1 plays a key role in podocyte gene-expression and subsequently in podocyte differentiation (Nachtigat et al 1998; Lefebvre et al. 2015).NoteDenys-Drash WT1 mutations are clustered particularly in the exons encoding Zf2 and Zf3in and behave as dominant negatives. Most WT1 mutations in rasier patients affect the exon 9 donor splice site resulting in a functional imbalance of WT1 +KTS isoforms, as detected on dysgenetic gonads by RTPCR (Klam et al.1998; Haber et al.1991). In addition transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) seems to have a more restrictive podocyte set of genes whose expression depends on these alternatively spliced isoforms (Klamt et al 1998; Lefebvre et al. 2015). To be noted Registryhttp:\/\/www.uke.de\/kliniken-institute\/kliniken\/kinder-und-jugendmedizin\/ Registry for Patients with WT1 Mutation Associated Diseases - UKE - Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Kinder- und Jugendmedizinhttps:\/\/www.amc.nl\/web\/Het-AMC\/Afdelingen\/Overzicht\/Klinische-Informatiekunde-KIK\/Klinische-Informatiekunde-KIK\/Department.htm ESPN\/ERA-EDTA Registry: European Registry for Children on Renal Replacement Therapy AMC - Academisch Medisch Centrum- Afdeling Klinische InformatiekundeDatabaseshttp:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=WT1 Gene WT1 (GeneCards)http:\/\/ghr.nlm.nih.gov\/condition\/denys-drash-syndrome Denys-Drash syndrome (Genetic Home Reference)BibliographyPubmed IDLast YearTitleAuthors219113222011Current concepts in disorders of sexual development.Öçal G et al182031542008Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.Antonius T et al93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al21725001990Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).Jadresic L et al94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al259933182015Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.Lefebvre J et al95901781998Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.Nachtigal MW et al169271062006WT1 and glomerular diseases.Niaudet P et al13275251992Inherited WT1 mutation in Denys-Drash syndrome.Coppes MJ et al16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al107622962000Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?Koziell A et al80719741994The Denys-Drash syndrome.Mueller RF et al External Links GARDERN GENTURISOMIMORPHANETMeSH Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Aditional Info × Loading, wait...
Mesothelioma, somatic
156240Nephrotic syndrome, type 4256370Wilms tumor, type 1194070AliasWilms Tumor 1NPHS4Last Three Zinc Fingers Of The DNA-Binding Domain Of WT1Amino-Terminal Domain Of EWSWilms Tumor ProteinEWS-WT1WIT-2AWT1WAGRGUDNoteWT1 gene encodes for a DNA-binding protein including four zinc-finger motifs at the C-terminus and a proline\/glutamine-rich DNA-binding domain at the N-terminus. It acts as trascriptional modulator that has an essential role in the normal development of the urogenital system. This gene has a biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues.Dna description10 exons, extending for 48 kb of genomic DNA.TranscriptionAlternative splicing at two sites results in four major different zinc finger protein isoforms (molecular weights of between 52 and 54 kDa).DescriptionAlternative splicing at the two sites generates 4 major different isoforms, respectively either including or excluding exon 5 and including or excluding three amino-acids - lysine, threonine and serine (KTS positive or negative isoforms). The KTS isoforms are highly conserved throughout evolution, indicating a very biological important function.ExpressionKidney, ovary, testis, liver, heart and hematopoietic cells.LocalisationMainly nuclear, depending on the different isoforms.FunctionWT1 mediates trascriptional activation and\/or repression of several gene targets. It particular seems to directly synergize with SF1 participating to steroidogenesis and in sexual differentiation by regulating expression of the polypeptide hormone mullerian inhibiting substance. In addition WT1 plays a key role in podocyte gene-expression and subsequently in podocyte differentiation (Nachtigat et al 1998; Lefebvre et al. 2015).NoteDenys-Drash WT1 mutations are clustered particularly in the exons encoding Zf2 and Zf3in and behave as dominant negatives. Most WT1 mutations in rasier patients affect the exon 9 donor splice site resulting in a functional imbalance of WT1 +KTS isoforms, as detected on dysgenetic gonads by RTPCR (Klam et al.1998; Haber et al.1991). In addition transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) seems to have a more restrictive podocyte set of genes whose expression depends on these alternatively spliced isoforms (Klamt et al 1998; Lefebvre et al. 2015). To be noted Registryhttp:\/\/www.uke.de\/kliniken-institute\/kliniken\/kinder-und-jugendmedizin\/ Registry for Patients with WT1 Mutation Associated Diseases - UKE - Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Kinder- und Jugendmedizinhttps:\/\/www.amc.nl\/web\/Het-AMC\/Afdelingen\/Overzicht\/Klinische-Informatiekunde-KIK\/Klinische-Informatiekunde-KIK\/Department.htm ESPN\/ERA-EDTA Registry: European Registry for Children on Renal Replacement Therapy AMC - Academisch Medisch Centrum- Afdeling Klinische InformatiekundeDatabaseshttp:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=WT1 Gene WT1 (GeneCards)http:\/\/ghr.nlm.nih.gov\/condition\/denys-drash-syndrome Denys-Drash syndrome (Genetic Home Reference)BibliographyPubmed IDLast YearTitleAuthors219113222011Current concepts in disorders of sexual development.Öçal G et al182031542008Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.Antonius T et al93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al21725001990Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).Jadresic L et al94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al259933182015Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.Lefebvre J et al95901781998Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.Nachtigal MW et al169271062006WT1 and glomerular diseases.Niaudet P et al13275251992Inherited WT1 mutation in Denys-Drash syndrome.Coppes MJ et al16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al107622962000Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?Koziell A et al80719741994The Denys-Drash syndrome.Mueller RF et al External Links GARDERN GENTURISOMIMORPHANETMeSH Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Aditional Info × Loading, wait...
Nephrotic syndrome, type 4
256370Wilms tumor, type 1194070AliasWilms Tumor 1NPHS4Last Three Zinc Fingers Of The DNA-Binding Domain Of WT1Amino-Terminal Domain Of EWSWilms Tumor ProteinEWS-WT1WIT-2AWT1WAGRGUDNoteWT1 gene encodes for a DNA-binding protein including four zinc-finger motifs at the C-terminus and a proline\/glutamine-rich DNA-binding domain at the N-terminus. It acts as trascriptional modulator that has an essential role in the normal development of the urogenital system. This gene has a biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues.Dna description10 exons, extending for 48 kb of genomic DNA.TranscriptionAlternative splicing at two sites results in four major different zinc finger protein isoforms (molecular weights of between 52 and 54 kDa).DescriptionAlternative splicing at the two sites generates 4 major different isoforms, respectively either including or excluding exon 5 and including or excluding three amino-acids - lysine, threonine and serine (KTS positive or negative isoforms). The KTS isoforms are highly conserved throughout evolution, indicating a very biological important function.ExpressionKidney, ovary, testis, liver, heart and hematopoietic cells.LocalisationMainly nuclear, depending on the different isoforms.FunctionWT1 mediates trascriptional activation and\/or repression of several gene targets. It particular seems to directly synergize with SF1 participating to steroidogenesis and in sexual differentiation by regulating expression of the polypeptide hormone mullerian inhibiting substance. In addition WT1 plays a key role in podocyte gene-expression and subsequently in podocyte differentiation (Nachtigat et al 1998; Lefebvre et al. 2015).NoteDenys-Drash WT1 mutations are clustered particularly in the exons encoding Zf2 and Zf3in and behave as dominant negatives. Most WT1 mutations in rasier patients affect the exon 9 donor splice site resulting in a functional imbalance of WT1 +KTS isoforms, as detected on dysgenetic gonads by RTPCR (Klam et al.1998; Haber et al.1991). In addition transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) seems to have a more restrictive podocyte set of genes whose expression depends on these alternatively spliced isoforms (Klamt et al 1998; Lefebvre et al. 2015). To be noted Registryhttp:\/\/www.uke.de\/kliniken-institute\/kliniken\/kinder-und-jugendmedizin\/ Registry for Patients with WT1 Mutation Associated Diseases - UKE - Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Kinder- und Jugendmedizinhttps:\/\/www.amc.nl\/web\/Het-AMC\/Afdelingen\/Overzicht\/Klinische-Informatiekunde-KIK\/Klinische-Informatiekunde-KIK\/Department.htm ESPN\/ERA-EDTA Registry: European Registry for Children on Renal Replacement Therapy AMC - Academisch Medisch Centrum- Afdeling Klinische InformatiekundeDatabaseshttp:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=WT1 Gene WT1 (GeneCards)http:\/\/ghr.nlm.nih.gov\/condition\/denys-drash-syndrome Denys-Drash syndrome (Genetic Home Reference)BibliographyPubmed IDLast YearTitleAuthors219113222011Current concepts in disorders of sexual development.Öçal G et al182031542008Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.Antonius T et al93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al21725001990Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).Jadresic L et al94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al259933182015Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.Lefebvre J et al95901781998Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.Nachtigal MW et al169271062006WT1 and glomerular diseases.Niaudet P et al13275251992Inherited WT1 mutation in Denys-Drash syndrome.Coppes MJ et al16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al107622962000Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?Koziell A et al80719741994The Denys-Drash syndrome.Mueller RF et al External Links GARDERN GENTURISOMIMORPHANETMeSH Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Aditional Info × Loading, wait...
Wilms tumor, type 1
194070AliasWilms Tumor 1NPHS4Last Three Zinc Fingers Of The DNA-Binding Domain Of WT1Amino-Terminal Domain Of EWSWilms Tumor ProteinEWS-WT1WIT-2AWT1WAGRGUDNoteWT1 gene encodes for a DNA-binding protein including four zinc-finger motifs at the C-terminus and a proline\/glutamine-rich DNA-binding domain at the N-terminus. It acts as trascriptional modulator that has an essential role in the normal development of the urogenital system. This gene has a biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues.Dna description10 exons, extending for 48 kb of genomic DNA.TranscriptionAlternative splicing at two sites results in four major different zinc finger protein isoforms (molecular weights of between 52 and 54 kDa).DescriptionAlternative splicing at the two sites generates 4 major different isoforms, respectively either including or excluding exon 5 and including or excluding three amino-acids - lysine, threonine and serine (KTS positive or negative isoforms). The KTS isoforms are highly conserved throughout evolution, indicating a very biological important function.ExpressionKidney, ovary, testis, liver, heart and hematopoietic cells.LocalisationMainly nuclear, depending on the different isoforms.FunctionWT1 mediates trascriptional activation and\/or repression of several gene targets. It particular seems to directly synergize with SF1 participating to steroidogenesis and in sexual differentiation by regulating expression of the polypeptide hormone mullerian inhibiting substance. In addition WT1 plays a key role in podocyte gene-expression and subsequently in podocyte differentiation (Nachtigat et al 1998; Lefebvre et al. 2015).NoteDenys-Drash WT1 mutations are clustered particularly in the exons encoding Zf2 and Zf3in and behave as dominant negatives. Most WT1 mutations in rasier patients affect the exon 9 donor splice site resulting in a functional imbalance of WT1 +KTS isoforms, as detected on dysgenetic gonads by RTPCR (Klam et al.1998; Haber et al.1991). In addition transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) seems to have a more restrictive podocyte set of genes whose expression depends on these alternatively spliced isoforms (Klamt et al 1998; Lefebvre et al. 2015). To be noted Registryhttp:\/\/www.uke.de\/kliniken-institute\/kliniken\/kinder-und-jugendmedizin\/ Registry for Patients with WT1 Mutation Associated Diseases - UKE - Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Kinder- und Jugendmedizinhttps:\/\/www.amc.nl\/web\/Het-AMC\/Afdelingen\/Overzicht\/Klinische-Informatiekunde-KIK\/Klinische-Informatiekunde-KIK\/Department.htm ESPN\/ERA-EDTA Registry: European Registry for Children on Renal Replacement Therapy AMC - Academisch Medisch Centrum- Afdeling Klinische InformatiekundeDatabaseshttp:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=WT1 Gene WT1 (GeneCards)http:\/\/ghr.nlm.nih.gov\/condition\/denys-drash-syndrome Denys-Drash syndrome (Genetic Home Reference)BibliographyPubmed IDLast YearTitleAuthors219113222011Current concepts in disorders of sexual development.Öçal G et al182031542008Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.Antonius T et al93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al21725001990Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).Jadresic L et al94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al259933182015Alternatively spliced isoforms of WT1 control podocyte-specific gene expression.Lefebvre J et al95901781998Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.Nachtigal MW et al169271062006WT1 and glomerular diseases.Niaudet P et al13275251992Inherited WT1 mutation in Denys-Drash syndrome.Coppes MJ et al16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al107622962000Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?Koziell A et al80719741994The Denys-Drash syndrome.Mueller RF et al External Links GARDERN GENTURISOMIMORPHANETMeSH Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Aditional Info × Loading, wait...