Predictive diagnosis of the cancer prone Li–Fraumeni syndrome by accident: new challenges through whole genome array testing
- T Schwarzbraun1,
- A C Obenauf1,
- A Langmann2,
- U Gruber-Sedlmayr3,
- K Wagner1,
- M R Speicher1,
- P M Kroisel1
- 1Institute of Human Genetics, Medical University of Graz, Graz, Austria
- 2Department of Ophthalmology, Medical University of Graz, Graz, Austria
- 3Department of Neuropediatrics, Medical University of Graz, Austria
- Professor M R Speicher, Institute of Human Genetics, Medical University of Graz, Harrachgasse 21/8, A-8010 Graz, Austria; michael.speicher{at}medunigraz.at
- Received 21 November 2008
- Revised 8 January 2009
- Accepted 27 January 2009
- Published Online First 5 March 2009
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.
Footnotes
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Funding: Work in our laboratory is supported by the European Commission (DISMAL project, contract no. LSHC-CT-2005-018911; GENINCA project, contract no. 202230) and the FWF (Austrian Science Fund). Anna C. Obenauf is funded by the PhD-Program Molecular Medicine of the Medical University of Graz.
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Competing interests: None.
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Patient consent: Obtained.
