Predictive diagnosis of the cancer prone Li-Fraumeni syndrome by accident: new challenges through whole genome array testing

J Med Genet. 2009 May;46(5):341-4. doi: 10.1136/jmg.2008.064972. Epub 2009 Mar 5.

Abstract

Background: Li-Fraumeni syndrome greatly increases the risk of developing several types of cancer and is usually caused by TP53 germline mutations. Predictive testing of at-risk family members is only offered after a complex genetic counselling process. Recently the clinical implementation of array comparative genomic hybridisation (CGH) has revolutionised the diagnosis of patients with syndromic or non-syndromic mental retardation and has evolved to a routinely performed high resolution whole genome scan.

Methods and results: When using array CGH to identify the cause for mental retardation in a 7-year-old child we found a submicroscopic de novo deletion of chromosome 17p13.1, which includes several genes likely to be causative for her phenotype, and also of TP53.

Conclusion: Thus, array CGH resulted in an unintended predictive diagnosis of an increased tumour susceptibility as observed in Li-Fraumeni syndrome.

Publication types

  • Case Reports
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child
  • Chromosome Breakage
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 17 / genetics
  • Comparative Genomic Hybridization / methods*
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • In Situ Hybridization, Fluorescence
  • Li-Fraumeni Syndrome / complications
  • Li-Fraumeni Syndrome / diagnosis
  • Li-Fraumeni Syndrome / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Tumor Suppressor Protein p53