Genotype/Phenotype Correlation in Nephrotic Syndrome Caused by WT1 Mutations
Genotype/Phenotype Correlation in Nephrotic Syndrome Caused by WT1 Mutations
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DOI：
10.2215/cjn.09351209
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发表时间：
2010-09-01
影响因子：
9.8
通讯作者：
Hildebrandt, Friedhelm
中科院分区：
文献类型：
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作者：
Chernin, Gil;Vega-Warner, Virginia;Hildebrandt, Friedhelm
背景和目的：由WT1突变引起的肾病综合征（NS）患者发生肾母细胞瘤（WT）的风险可能存在，也可能不存在。本文描述了来自51个因WT1突变而患有NS的家庭的52名患者的WT结局和风险的基因型/表型相关性。设计、设置、参与者和测量：本研究随访了19例内含子9剪接供体位点突变（KTS突变）患者、27例错义突变患者、4例无义突变患者、1例内含子8剪接位点突变患者和1例缺失患者。结果：检测到24种不同的WT1突变。19例KTS突变患者中有16例为女性。核型为46、XX者为分离性NS，核型为46、XY者为Frasier综合征。与错义突变相比，KTS突变患者的年龄明显变大，并且向慢性肾脏疾病（CKD） 5期进展较慢。无义突变患者最初表现为WT。6例有错义突变的患者在诊断为NS后发展为WT（从NS发病到WT的间隔为0.1 ~ 1.4年）。结论：(1)在46，XX例女性中，KTS突变导致分离性NS，但不存在WT。(2)在46例XY型女性中，KTS突变导致Frasier综合征伴性腺母细胞瘤风险。(3)与错义突变相比，KTS突变引起NS的进展较慢。(4)有无WT均可发生错义突变。(5)WT1分析对年轻NS患者的早期发现和肿瘤预防具有重要意义。中国临床医学杂志，2010,31(5):555 - 562。doi: 10.2215 / CJN.09351209
Background and objectives: 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.Results: 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).Conclusions: (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. Clin J Am Soc Nephrol 5: 1655-1662, 2010. doi: 10.2215/CJN.09351209