A novel WT1 missense mutation presenting with Denys–Drash syndrome and cortical atrophy

Abstract

Germline heterozygous missense mutations in the Wilms’ tumour suppressor gene 1 (WT1) cause Denys–Drash Syndrome (DDS), which is characterized by a progressive glomerulopathy (mainly diffuse mesangial sclerosis), genital abnormalities in genotypic males and a predisposition to Wilms’ tumour [1]. The protein exerts its function as a tissue-specific zinc finger transcription factor by binding to the promoter of its target genes and, thus, regulating their transcription. Loss of WT1 function through mutations results in the misregulation of these target genes and, subsequently, in developmental defects. The expression pattern of WT1 mRNA together with data obtained from WT1 deficient mice indicate that the function of the gene is not restricted to the urogenital system, but involves the development of other organs, such as spleen, adrenal glands, heart, mesothelium, spinal cord and brain [2–5]. We report a novel germline WT1 missense mutation in a genotypic male patient with DDS and cerebral atrophy.