title: Clinical Aspects of WT1 and the Kidney.
abstract: For more than 30 years, WT1 mutations have been associated with complex developmental syndromes involving the kidney. Acting as a transcription factor, WT1 is expressed throughout the nephron and controls the reciprocal interactions and phenotypic changes required for normal renal development. In the adult, WT1 expression remains extremely high in the renal podocyte, and at a lower level in the parietal epithelial cells. Wt1-null mice are unable to form kidneys [1]. Unsurprisingly, WT1 mutations lead to significant abnormalities of the renal and genitourinary tract, causing a number of human diseases including syndromes such as Denys-Drash syndrome, Frasier syndrome, and WAGR syndrome. Recent methodological advances have improved the identification of WT1 mutations, highlighting its importance even in nonsyndromic renal disease, particularly in steroid-resistant nephrotic syndrome. This vast spectrum of WT1-related disease typifies the varied and complex activity of WT1 in development, disease, and tissue maintenance.
authors.affiliation: ECAT Clinical Lecturer-Nephrology, IGMM Human Genetics Unit, Western General Hospital, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK. Eve.miller-hodges@ed.ac.uk.
authors.forename: Eve
authors.initials: E
authors.lastname: Miller-Hodges
mesh_terms: D030321:Denys-Drash Syndrome / Q000235:genetics; D005260:Female; D052159:Frasier Syndrome / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA; D017624:WAGR Syndrome / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism*; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Genetic testing; Genitourinary syndromes; Glomerular sclerosis; Mesangial cells; Nephrotic syndrome; Renal podocyte; Transplantation