An intronic polymorphic deletion in the PTEN gene: implications for molecular diagnostic testing
S Sandell1, R J L Schuit, D J Bunyan
1Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK.
British Journal of Cancer
|January 10, 2013
Summary
A common PTEN gene deletion, initially detected in patients with suspected genetic syndromes, was found to be a benign polymorphism. This 899 bp deletion impacts PCR testing but has no clinical significance.
Area of Science:
- Genetics
- Molecular Biology
- Clinical Diagnostics
Background:
- Investigated PTEN gene mutations in 629 patients with suspected Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome.
- Focused on identifying genetic alterations within the PTEN gene.
Purpose of the Study:
- To analyze PTEN gene mutations in a patient cohort.
- To characterize a specific deletion variant within the PTEN gene.
- To determine the clinical relevance of the identified PTEN deletion.
Main Methods:
- Utilized multiplex ligation-dependent probe amplification (MLPA) for PTEN gene dosage analysis.
- Employed direct sequencing for PTEN point mutation analysis.
- Sequenced an 899 bp deletion variant in the PTEN gene.
Main Results:
- Identified an 899 bp deletion in PTEN intron 1 in approximately 4% of patients and 3% of controls.
- The deletion removes MLPA probe-binding sites and is located near exon 2.
- This deletion was also observed in patients with other causative PTEN mutations.
Conclusions:
- The 899 bp PTEN deletion is likely a benign polymorphism with no clinical effect.
- The deletion interferes with PCR-based PTEN testing by removing primer binding sites.
- This finding highlights potential artifacts in genetic testing for PTEN-related disorders.
