Santín S, Fraga G, Ruíz P, Pardo N, Torrent M, Martí T, Ballarín J, Ars E, Torra R
Molecular Biology Laboratory, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
Clin Nephrol. 2011 Sep;76(3):244-8. doi: 10.5414/cn106869.
Wilms' tumor suppressor gene (WT1) encodes a transcription factor required for normal development of the genitourinary system. Germline WT1 mutations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms' tumor. Here we report a 4-year-old male patient who presented with bilateral cryptorchidism, Wilms' tumor, nephroblastomatosis and renal failure without nephrotic proteinuria. Sequence analysis of the WT1 gene demonstrated a constitutional heterozygous nonsense mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc-finger 1. In the DNA of the tumor, we observed the same mutation in homo/hemizygosity. Given the requirement of WT1 for normal development, the WT1 mutation is likely to be responsible for the nephroblastomatosis and, in consequence, for the severe renal failure observed in our patient. This finding extends the spectrum of kidney diseases related to WT1 mutations and points to the need to screen for this gene in children with genitourinary abnormalities and Wilms' tumor because of the associated risk of nephroblastomatosis and renal failure in those carrying WT1 mutations.
肾母细胞瘤抑癌基因（WT1）编码一种泌尿生殖系统正常发育所需的转录因子。种系WT1突变已在多种病理状况中被描述，包括肾脏疾病、生殖器异常和肾母细胞瘤。在此，我们报告一名4岁男性患者，其表现为双侧隐睾、肾母细胞瘤、肾母细胞增殖症和肾衰竭，但无肾病性蛋白尿。WT1基因的序列分析显示外显子7存在一个组成性杂合无义突变，这导致WT1蛋白在锌指1处截短。在肿瘤的DNA中，我们观察到该突变呈纯合/半合子状态。鉴于WT1对正常发育的需求，WT1突变很可能是肾母细胞增殖症的病因，进而导致了我们患者所观察到的严重肾衰竭。这一发现扩展了与WT1突变相关的肾脏疾病谱，并指出由于携带WT1突变的患者存在肾母细胞增殖症和肾衰竭的相关风险，对于患有泌尿生殖系统异常和肾母细胞瘤的儿童有必要筛查该基因。
