Search our Database of Scientific Publications and Authors

I’m looking for a
    Hemolytic uremic syndrome as the presenting manifestation of WT1 mutation and Denys-Drash syndrome: a case report.
    BMC Nephrol 2017 Jul 18;18(1):243. Epub 2017 Jul 18.
    Baylor College of Medicine, Department of Pediatrics, Renal Section, Houston, TX, USA.
    Background: Hemolytic uremic syndrome (HUS) can occur as a primary process due to mutations in complement genes or secondary to another underlying disease. HUS sometimes occurs in the setting of glomerular diseases, and it has been described in association with Denys-Drash syndrome (DDS), which is characterized by the triad of abnormal genitourinary development; a pathognomonic glomerulopathy, diffuse mesangial sclerosis; and the development of Wilms tumor.

    Case Presentation: We report the case of a 46, XX female infant who presented with HUS and biopsy-proven thrombotic microangiopathy. Next generation sequencing of genes with known mutations causative of atypical HUS found that she was homozygous for the Complement Factor H H3 haplotype and heterozygous for a variant of unknown significance in the DGKE gene. Whole exome sequencing identified a de novo heterozygous WT1 c.1384C > T; p.R394W mutation, which is classically associated with Denys-Drash syndrome (DDS). At the time of bilateral nephrectomy five months after her initial biopsy, she had diffuse mesangial sclerosis, typical of Denys-Drash syndrome, without evidence of thrombotic microangiopathy.

    Conclusion: This unique case highlights HUS as a rare but important manifestation of WT1 mutation and provides new insight into the genetics underlying this association.

    Similar Publications

    Hemolytic uremic syndrome associated with Denys-Drash syndrome.
    Pediatr Nephrol 2000 Oct;14(12):1092-7
    Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania, 19104, USA.
    The Denys-Drash syndrome is defined by the occurrence of combinations of pseudohermaphroditism, nephrotic syndrome with diffuse mesangial sclerosis, Wilms' tumor, and constitutional mutations in the WT1 suppressor gene. Most patients develop end-stage renal failure. Atypical hemolytic uremic syndrome (HUS) is defined by onset of acute hemolytic anemia with fragmented erythrocytes, thrombocytopenia, and renal failure in the absence of a gastrointestinal prodromal illness of bloody diarrhea. Read More
    WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis.
    Am J Pathol 1999 Jan;154(1):181-92
    INSERM U.423, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
    Denys-Drash syndrome is a rare disorder of urogenital development characterized by the association of early onset glomerulopathy caused by diffuse mesangial sclerosis, gonadal dysgenesis leading to pseudohermaphroditism in males, and a high risk of developing Wilms' tumor. The syndrome is caused by dominant negative point mutations in the WT1 gene that encodes a tumor suppressor transcription factor normally expressed in podocytes. Mutations usually affect the zinc fingers of the WT1 protein. Read More
    Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome.
    Pediatr Nephrol 2001 Aug;16(8):627-30
    Division of Pediatric Nephrology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA.
    We report the identification of a novel Wilms tumor suppressor gene mutation in a 5-month-old girl who presented with unilateral Wilms tumor (WT) and renal diffuse mesangial sclerosis typical of Denys-Drash syndrome (DDS). The patient did not have ambiguous genitalia and the karyotype (by amniocentesis) was 46, XX. A de novo constitutional heterozygous mutation in WT1 gene exon 9 coding for the third zinc-finger (1163G-->A, C388Y) was identified. Read More
    A familial WT1 mutation associated with incomplete Denys-Drash syndrome.
    Eur J Pediatr 2013 Oct 29;172(10):1357-62. Epub 2013 May 29.
    Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
    Unlabelled: Denys-Drash syndrome (DDS) is a rare disorder characterized by nephropathy, male pseudohermaphroditism, and wilms tumor. Cases are thought to arise sporadically through a de novo mutation in the wilms tumor suppressor gene (WT1), which encodes a zinc finger protein that not only acts as a tumor suppressor but is essential for normal gonadogenesis, nephrogenesis, and development of the urogenital tract. In this report, we describe a family with the well-known missense mutation in exon 9 of the WT1 gene, 1180C>T (R394W), causing incomplete DDS and no symptoms in their father. Read More