Wilms tumor arising in a child with X-linked nephrogenic diabetes insipidus.
We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.
El-Kares
Reyhan
R
Department of Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste Catherine west, Montreal, Quebec, Canada.
Hueber
Pierre-Alain
PA
Blumenkrantz
Miriam
M
Iglesias
Diana
D
Ma
Kim
K
Jabado
Nada
N
Bichet
Daniel G
DG
Goodyer
Paul
P
D001483:Base Sequence; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D018500:Diabetes Insipidus, Nephrogenic / Q000150:complications* / Q000235:genetics / Q000473:pathology; D016162:Genes, Wilms Tumor; D040181:Genetic Diseases, X-Linked / Q000150:complications* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D017483:Receptors, Vasopressin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000150:complications* / Q000235:genetics / Q000473:pathology; D051176:beta Catenin / Q000235:genetics
C495270:CTNNB1 protein, human; D017483:Receptors, Vasopressin; D051176:beta Catenin