title: An intronic polymorphic deletion in the PTEN gene: implications for molecular diagnostic testing.
abstract: BACKGROUND
  A cohort of 629 patients with suspected Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome was tested for mutations in the PTEN gene.
  
  
  METHODS
  Dosage analysis of PTEN was carried out using a PTEN-specific multiplex ligation-dependent probe amplification (MLPA) kit, whereas point mutation analysis was performed using direct sequencing.
  
  
  RESULTS
  Approximately 4% of the patients from the testing cohort were heterozygously deleted for the two MLPA probe-binding sites situated in intron 1. The same deletion was subsequently seen in ∼3% of 220 normal controls, and in patients from the testing cohort with a causative mutation elsewhere in the PTEN gene. Sequencing of the variant revealed an 899 bp deletion, the 3' breakpoint of which is only 58 bp from the start of exon 2.
  
  
  CONCLUSIONS
  Although all evidence suggests that the 899 bp deletion is a polymorphism with no clinical effect, it removes the binding sites of almost all published PTEN exon 2 forward primers, resulting in allelic loss during PCR.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sandell
authors.forename: R J L
authors.initials: RJ
authors.lastname: Schuit
authors.forename: D J
authors.initials: DJ
authors.lastname: Bunyan
mesh_terms: D004252:DNA Mutational Analysis; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D025202:Molecular Diagnostic Techniques; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human