Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations
Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations
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DOI：
10.1046/j.1523-1755.1998.00948.x
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发表时间：
1998-06-01
影响因子：
19.6
通讯作者：
Royer-Pokora, B
中科院分区：
文献类型：
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作者：
Schumacher, V;Schärer, K;Royer-Pokora, B
我们调查了17例儿童肾病综合征（NS）的早期发病（14例年龄< 1岁），并迅速进展为终末期肾病，以确定是否存在11号染色体上Wilms肿瘤抑制基因WT 1突变。在8名儿童（7名基因型男性）中观察到与肾母细胞瘤和/或不明生殖器（Denys-Drash综合征）相关。在这8例和另外2例女性NS患者中，仅检测到WT 1基因的组成性错义突变; 4例儿童在外显子9（R394 N）中出现所谓的热点突变，6例在外显子8和9中出现不同的突变（4例先前未描述）。肾活检示弥漫性系膜硬化8例，局灶性节段性硬化2例。10例患者中有7例在NS发作后4个月内或同时出现终末期肾病。在4名儿童（3名男性，1名女性）中，在NS之前或同时发现了单侧Wilms肿瘤。从7个基因型男性WT 1突变，五个模糊的生殖器和两个女性表型。在其他7名患有孤立性先天性或婴儿NS伴或不伴DMS的儿童中未发现WT 1基因突变，这些儿童的进展似乎比第一组慢。建议对早期发病、快速进展的NS和弥漫性系膜或局灶性节段性硬化的患者进行WT 1突变检测，以确定发生肾母细胞瘤的风险。
We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged < 1 year) and rapid progression to end-stage renal disease for the presence of mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight children (7 genotypic males) an association with Wilms' tumor and/or ambiguous genitalia (Denys-Drash syndrome) was observed. In these eight and two additional female patients with NS only constitutional missense mutations in the WT1 gene were detected; four children presented the so-called hot spot mutation in exon 9 (R394N) and six had different mutations in exons 8 and 9 (4 not previously described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal segmental sclerosis in two cases. End-stage renal disease was reached either concomitantly or within four months after onset of NS in seven of ten patients. A unilateral Wilms' tumor was found before or concomitant with NS in four children (3 males, 1 female). From the seven genotypic males with WT1 mutations, five presented ambiguous genitalia and two a female phenotype. No mutation of the WT1 gene was found in seven other children with isolated congenital or infantile NS with or without DMS who appeared to have a slower progression than the first group. It is proposed that patients with early onset, rapidly progressive NS and diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations to identify those at risk for developing Wilms' tumor.