Kaltenis Petras, Schumacher Valérie, Jankauskiene Augustina, Laurinavicius Arvydas, Royer-Pokora Brigitte
Vilnius University Children's Hospital, Vilnius, Lithuania.
Pediatr Nephrol. 2004 Mar;19(3):353-6. doi: 10.1007/s00467-003-1372-1. Epub 2004 Jan 27.
Constitutional missense mutations in the WT1 gene are usually associated with the Denys-Drash syndrome, characterized by a rapid progressive nephropathy, male pseudohermaphroditism, and an increased risk for Wilms tumor. We report here a patient with scrotal hypospadias and a slow progressive nephropathy due to focal and segmental glomerulosclerosis. WT1 mutation analysis revealed a constitutional missense mutation in exon 9 resulting in an exchange F392L. This mutation has previously been reported by others in a patient with a similar mild course of nephropathy. In contrast, a mutation in the corresponding codon of exon 8 (F364L) was previously found by us in a patient with a very rapid progression to end-stage renal disease. Whether the position of a mutation may influence the course of the nephropathy must be evaluated in a larger patient cohort. The individual tumor risk for this alteration cannot be given at present because neither of the two patients has shown evidence of a Wilms tumor or a gonadoblastoma to date.
WT1基因的先天性错义突变通常与迪尼-德拉斯综合征相关，其特征为快速进展性肾病、男性假两性畸形以及患威尔姆斯瘤的风险增加。我们在此报告一名患有阴囊型尿道下裂和因局灶节段性肾小球硬化导致的缓慢进展性肾病的患者。WT1突变分析显示外显子9存在先天性错义突变，导致F392L替换。此前其他研究人员曾在一名患有类似轻度肾病病程的患者中报告过此突变。相比之下，我们之前在一名迅速进展至终末期肾病的患者中发现外显子8相应密码子的突变（F364L）。突变位置是否会影响肾病病程必须在更大的患者队列中进行评估。目前无法给出这种改变的个体肿瘤风险，因为这两名患者迄今均未显示出威尔姆斯瘤或性腺母细胞瘤的证据。
