Discordant expression of a new WT1 gene mutation in a family with monozygotic twins presenting with congenital nephrotic syndrome
Discordant expression of a new WT1 gene mutation in a family with monozygotic twins presenting with congenital nephrotic syndrome
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DOI：
10.1007/s00431-011-1497-3
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发表时间：
2012-01-01
影响因子：
3.6
通讯作者：
Blahova, Kveta
中科院分区：
文献类型：
--
作者：
Fencl, Filip;Malina, Michal;Blahova, Kveta
先天性肾病综合征（congenitalnephropathicsyndrome，CNS）是一组病因和表现各异的疾病.三分之二的出生后第一年NS病例是由四种基因（NPHS 1、NPHS 2、WT 1和LAMB 2）突变引起的。WT 1基因突变可导致Denys-Drash综合征（DDS）。我们报告一对患有中枢神经系统的女性单卵双胞胎，在7周和8周时出现无尿性肾功能衰竭。双胞胎均接受腹膜透析治疗。肾活检证实弥漫性系膜硬化。遗传分析发现一个新的杂合子WT 1突变R434 P在这两个双胞胎。一个孩子患了单侧肾母细胞瘤。这对双胞胎分别在23周/13.5个月时死于CNS并发症（脓毒症和中心静脉系统广泛血栓形成/脓毒症和突发心力衰竭）。DNA分析显示，父亲也有相同的WT 1突变，他在41岁时没有表现出这种突变的临床后果，也没有DDS的迹象。总之，我们报告了第三个家庭与单卵双胞胎DDS由于WT 1突变。DDS非常迅速地导致双胞胎的终末期肾衰竭和死亡，这与他们父亲的表现形成鲜明对比。
Congenital nephrotic syndrome (CNS) is a heterogeneous group of diseases with different causes and prognoses. Two thirds of cases of NS in the first year of life are caused by mutations in four genes (NPHS1, NPHS2, WT1, and LAMB2). The mutation of WT1 gene can lead to Denys-Drash syndrome (DDS). We report on female monozygotic twins with CNS presenting at 7 and 8 weeks of age with anuric renal failure. Both twins were treated by peritoneal dialysis. Renal biopsy proved diffuse mesangial sclerosis. Genetic analysis detected a new heterozygote WT1 mutation R434P in both twins. One child developed a unilateral nephroblastoma. Both twins died because of complications of CNS (sepsis and extensive thrombosis of central venous system/sepsis and sudden heart failure) at ages 23 weeks/13.5 months, respectively. DNA analysis showed the same WT1 mutation in the father, who showed at his age of 41 years no clinical consequences of this mutation and no signs of DDS. In conclusion, we report the third family with monozygotic twins with DDS due to WT1 mutation. The DDS has very rapidly led to end-stage renal failure and death in both twins which is in striking contrast to the manifestation in their father.