Departments of Pediatrics, University of Michigan Health System, Ann Arbor, MI 48109-5646, USA.
Clin J Am Soc Nephrol. 2010 Sep;5(9):1655-62. doi: 10.2215/CJN.09351209. Epub 2010 Jul 1.
The risk of developing Wilms tumor (WT) can be present or absent in patients with nephrotic syndrome (NS) caused by WT1 mutations. Here, the genotype/phenotype correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study followed 19 patients with mutations in intron 9 splice donor site (KTS mutations), 27 patients with missense mutations, 4 patients with nonsense mutations, 1 patient with a splice site mutation in intron 8, and 1 patient with a deletion.
Twenty-four different WT1 mutations were detected. Sixteen of the 19 patients with KTS mutations were females. These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY. Patients with KTS mutations presented at a significantly older age and with a slower progression toward chronic kidney disease (CKD) stage 5, compared with missense mutations. Patients with nonsense mutations presented initially with WT. Six patients with missense mutations developed WT after the diagnosis of NS (interval-range from NS onset to WT of 0.1 to 1.4 years).
(1) KTS mutations cause isolated NS with absence of WT in 46,XX females. (2) KTS mutations cause Frasier syndrome with gonadoblastoma risk in 46,XY phenotypic females. (3) KTS mutations cause NS with a slower progression when compared with missense mutations. (4) Missense mutations can occur with and without WT. (5) WT1 analysis is important in young patients with NS for early detection and tumor prophylaxis.
WT1 基因突变导致的肾病综合征（NS）患者存在或不存在发生 Wilms 肿瘤（WT）的风险。在此，描述了 51 个 WT1 基因突变导致 NS 的家系中 52 名患者的基因型/表型相关性及其 WT 结局和风险。
设计、设置、参与者和测量：本研究随访了 19 名存在内含子 9 剪接供体位点（KTS 突变）突变的患者、27 名存在错义突变的患者、4 名存在无义突变的患者、1 名存在内含子 8 剪接位点突变的患者和 1 名存在缺失的患者。
检测到 24 种不同的 WT1 突变。19 名 KTS 突变患者中，有 16 名为女性。如果核型为 46,XX，则这些患者存在孤立性 NS，如果核型为 46,XY，则存在 Frasier 综合征。KTS 突变患者发病年龄较大，且向慢性肾脏病（CKD）5 期进展较慢，而错义突变患者则相反。无义突变患者最初表现为 WT。6 名存在错义突变的患者在 NS 诊断后发展为 WT（从 NS 发病到 WT 的时间间隔范围为 0.1 至 1.4 年）。
（1）KTS 突变导致 46,XX 女性存在孤立性 NS，而不存在 WT。（2）KTS 突变导致 46,XY 表型女性存在 Frasier 综合征和性腺母细胞瘤风险。（3）与错义突变相比，KTS 突变导致 NS 进展较慢。（4）错义突变可伴有或不伴有 WT。（5）WT1 分析对存在 NS 的年轻患者非常重要，可早期发现并进行肿瘤预防。
