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Discordant expression of a new WT1 gene mutation in a family with monozygotic twins presenting with congenital nephrotic syndrome

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Abstract

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.

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Acknowledgments

This work was supported by grant GAUK (Grant Agency of the Charles University) No. 910 10 and grant of the Ministry of Health Czech Republic VZ No. 0006420301. We would like to thank Dr. Beata Lipska, Ph.D. for the help with correct nomenclature of WT1 mutations.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Úvalu 84, 150 06, Prague 5, Czech Republic

    Filip Fencl, Michal Malina, Veronika Stará, Jakub Zieg, Tomáš Seeman & Květa Bláhová

  2. Department of Anesthesiology and Resuscitation 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Úvalu 84, 150 06, Prague 5, Czech Republic

    Dana Mixová

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  1. Filip Fencl
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  2. Michal Malina
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  3. Veronika Stará
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Correspondence to Filip Fencl.

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Fencl, F., Malina, M., Stará, V. et al. Discordant expression of a new WT1 gene mutation in a family with monozygotic twins presenting with congenital nephrotic syndrome. Eur J Pediatr 171, 121–124 (2012). https://doi.org/10.1007/s00431-011-1497-3

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  • DOI: https://doi.org/10.1007/s00431-011-1497-3

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