Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype
Abstract Introduction Wilms tumor 1 (WT1)-related disorders are a group of hereditary disorders caused by alterations in the WT1 gene. WT1 expression is critical for the maturation of many organs, such as the gonads, kidneys, and spleen. WT1 variants might lead to nephrotic syndromes or disorders in...
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| Format: | Article |
| Language: | English |
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Springer
2025-03-01
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| Series: | Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1007/s44162-025-00070-5 |
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| author | Heba A. Hassan Inas Mazen Mona K. Mekkawy Aya Elaidy Alaa Kamel Mona L. Essawi |
| author_facet | Heba A. Hassan Inas Mazen Mona K. Mekkawy Aya Elaidy Alaa Kamel Mona L. Essawi |
| author_sort | Heba A. Hassan |
| collection | DOAJ |
| description | Abstract Introduction Wilms tumor 1 (WT1)-related disorders are a group of hereditary disorders caused by alterations in the WT1 gene. WT1 expression is critical for the maturation of many organs, such as the gonads, kidneys, and spleen. WT1 variants might lead to nephrotic syndromes or disorders in gonadal development. Objective An observational study has been established. Cytogenetic and molecular studies were performed on a patient with urogenital impairments to identify the underlying genetic cause. Methods Fluorescence in situ hybridization (FISH) was conducted on gonadal cell culture at the centromeric region of both X and Y chromosomes. Exome sequencing and segregation analysis by Sanger sequencing of the WT1 gene coding exon for the patient and the parents have been done. Computational studies were performed to predict the effect of novel variants. Results The studied patient had a de novo heterozygous novel variant in the WT1 gene. Mixed gonadal dysgenesis (MGD) was also detected, in addition to the heterozygous (p.K464R) novel variant in the WT1 gene. Conclusion Pathogenic variants in the WT1 gene cause a wide range of phenotypes and allelic syndromes that could be related to the multiple isoforms produced. Sequencing of the WT1 gene can efficiently diagnose patients with 46,XY DSD, and renal anomalies. More research is required to identify the genetic basis of primary, undefined ureteropelvic junction obstruction. Follow-up is essential in WT1-related disorders to prevent tumor development and/or end-stage renal failure progression. |
| format | Article |
| id | doaj-art-2f5aadd44ecf497ca3c938eabac6f516 |
| institution | OA Journals |
| issn | 2731-085X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Rare Diseases |
| spelling | doaj-art-2f5aadd44ecf497ca3c938eabac6f5162025-08-20T01:57:40ZengSpringerJournal of Rare Diseases2731-085X2025-03-01411710.1007/s44162-025-00070-5Novel variant in WT1 gene associated with MGD and unique kidney disease phenotypeHeba A. Hassan0Inas Mazen1Mona K. Mekkawy2Aya Elaidy3Alaa Kamel4Mona L. Essawi5Department of Medical Molecular Genetics, Human Genetics & Genome Research Institute, National Research CentreDepartment of Clinical Genetics, Human Genetics & Genome Research Institute, National Research CentreDepartment of Human Cytogenetics, Human Genetics & Genome Research Institute, National Research CentreDepartment of Clinical Genetics, Human Genetics & Genome Research Institute, National Research CentreDepartment of Human Cytogenetics, Human Genetics & Genome Research Institute, National Research CentreDepartment of Medical Molecular Genetics, Human Genetics & Genome Research Institute, National Research CentreAbstract Introduction Wilms tumor 1 (WT1)-related disorders are a group of hereditary disorders caused by alterations in the WT1 gene. WT1 expression is critical for the maturation of many organs, such as the gonads, kidneys, and spleen. WT1 variants might lead to nephrotic syndromes or disorders in gonadal development. Objective An observational study has been established. Cytogenetic and molecular studies were performed on a patient with urogenital impairments to identify the underlying genetic cause. Methods Fluorescence in situ hybridization (FISH) was conducted on gonadal cell culture at the centromeric region of both X and Y chromosomes. Exome sequencing and segregation analysis by Sanger sequencing of the WT1 gene coding exon for the patient and the parents have been done. Computational studies were performed to predict the effect of novel variants. Results The studied patient had a de novo heterozygous novel variant in the WT1 gene. Mixed gonadal dysgenesis (MGD) was also detected, in addition to the heterozygous (p.K464R) novel variant in the WT1 gene. Conclusion Pathogenic variants in the WT1 gene cause a wide range of phenotypes and allelic syndromes that could be related to the multiple isoforms produced. Sequencing of the WT1 gene can efficiently diagnose patients with 46,XY DSD, and renal anomalies. More research is required to identify the genetic basis of primary, undefined ureteropelvic junction obstruction. Follow-up is essential in WT1-related disorders to prevent tumor development and/or end-stage renal failure progression.https://doi.org/10.1007/s44162-025-00070-5WT1 geneMixed gonadal dysgenesis46XY DSDUreteropelvic junction obstructionExome sequencing |
| spellingShingle | Heba A. Hassan Inas Mazen Mona K. Mekkawy Aya Elaidy Alaa Kamel Mona L. Essawi Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype Journal of Rare Diseases WT1 gene Mixed gonadal dysgenesis 46 XY DSD Ureteropelvic junction obstruction Exome sequencing |
| title | Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype |
| title_full | Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype |
| title_fullStr | Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype |
| title_full_unstemmed | Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype |
| title_short | Novel variant in WT1 gene associated with MGD and unique kidney disease phenotype |
| title_sort | novel variant in wt1 gene associated with mgd and unique kidney disease phenotype |
| topic | WT1 gene Mixed gonadal dysgenesis 46 XY DSD Ureteropelvic junction obstruction Exome sequencing |
| url | https://doi.org/10.1007/s44162-025-00070-5 |
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