Germline DICER1 mutations and familial cystic nephroma

J Med Genet. 2010 Dec;47(12):863-6. doi: 10.1136/jmg.2010.081216. Epub 2010 Oct 29.

Abstract

Background: Multilocular cystic nephroma (CN) is a benign kidney tumour and is part of a family of kidney neoplasms including cystic partially differentiated nephroblastoma and Wilms tumour (WT). CN is rarely familial or bilateral, but it occurs in about 10% of families where pleuropulmonary blastoma (PPB) is present. Recently, germline mutations in DICER1 were found in familial PPB.

Objective: To search for DICER1 mutations in two families with familial CN; PPB was present in one family. Additionally, to test germline DNA from 50 children with sporadic WT for DICER1 mutations.

Results: Both families with multiple CN were found to have mutations in DICER1 leading to premature stop codons, predicted to result in loss of the ribonuclease and dsRNA binding domains. These domains are essential to the function of DICER1. No germline mutations were found in any of the 50 children who had developed WT.

Conclusion: It has been established that DICER1 mutations cause familial CN and may be implicated in bilateral CN. No germline mutations were found in the patients with WT, suggesting that DICER1 mutations are unlikely to have a major role in the aetiology of sporadic WT. These results provide further evidence implicating miRNA dysregulation in tumourigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases / genetics*
  • DNA Mutational Analysis
  • Family
  • Female
  • Germ-Line Mutation / genetics*
  • Humans
  • Infant
  • Kidney Diseases, Cystic / complications*
  • Kidney Diseases, Cystic / genetics*
  • Kidney Diseases, Cystic / pathology
  • Kidney Neoplasms / complications*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Pedigree
  • Ribonuclease III / genetics*
  • Young Adult

Substances

  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases