An intronic polymorphic deletion in the PTEN gene: implications for molecular diagnostic testing.

[cowden syndrome]

A cohort of 629 patients with suspected Bannayan-Riley -Ruvalcaba syndrome or Cowden syndrome was tested for mutations in the PTEN gene .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 .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 .A lthough 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 .