WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, wilms tumor and cerebellar angioblastoma

Gergely Buglyó, G. Méhes, György Vargha, Sándor Biró, J. Mátyus

Research output: Contribution to journalArticle

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Abstract

The Wilms tumor 1 (WT1) gene is currently in focus by pediatric nephrologists as its mutations are associated with nephrotic syndrome, especially as part of complex clinical entities like Denys-Drash or Frasier syndrome. Renal failure may also develop in young WAGR patients, whose condition is attributed to a deletion at chromosomal region 11p13. However, only limited data exist on WT1 microdeletions. A 30-year-old male patient, with a history of genital malformations, a Wilms tumor manifested during the treatment of acute lymphoid leukemia (ALL) at the age of 4, and a cerebellar angioblastoma, was referred with proteinuria and a reduced glomerular filtration rate (GFR). Kidney biopsy revealed FSGS. Although all WT1 exons were amplified with polymerase chain reaction (PCR) and sequenced, none of them showed a mutation. However, an formalin-fixed, paraffin- embedded (FFPE) tissue sample of the patient's childhood Wilms tumor showed WT1- positivity restricted to the renal tumor cells, so the WT1 gene was investigated further. Using quantitative reverse transcription PCR (qRT-PCR), the gene was found to be present in only one copy in the patient's genomic DNA sample, while both copies were detected in both parents. In the patient's sister, the proximal region of WT1 was shown to have an extra copy. Evidence suggests that a heterozygous microdeletion of the gene WT1 is responsible for the patient's disease. It seems reasonable to assume a possible abnormality affecting meiotic crossing over at the WT1 locus in one of the parents.

Original languageEnglish
Pages (from-to)414-418
Number of pages5
JournalClinical Nephrology
Volume79
Issue number5
DOIs
Publication statusPublished - May 2013

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XY Disorders of Sex Development 46
Focal Segmental Glomerulosclerosis
Wilms Tumor
Leukemia
Wilms' Tumor Genes
Frasier Syndrome
Denys-Drash Syndrome
Parents
Kidney
Polymerase Chain Reaction
Mutation
Nephrotic Syndrome
Glomerular Filtration Rate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proteinuria
Paraffin
Formaldehyde
Genes
Reverse Transcription
Renal Insufficiency

Keywords

  • Focal segmental glomerulosclerosis
  • Leukemia
  • Microdeletion
  • Pseudohermaphroditism
  • Wilms tumor 1

ASJC Scopus subject areas

  • Nephrology

Cite this

WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, wilms tumor and cerebellar angioblastoma. / Buglyó, Gergely; Méhes, G.; Vargha, György; Biró, Sándor; Mátyus, J.

In: Clinical Nephrology, Vol. 79, No. 5, 05.2013, p. 414-418.

Research output: Contribution to journalArticle

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