Background-Juvenile polyposis syndrome (JPS) is characterised by gastrointe
stinal (GI) hamartomatous polyposis and an increased risk of GI malignancy.
Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (B
RRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because i
t relies on exclusion of CS, ERRS, and GS. Germline mutations in the PTCH,
PTEN and DPC4 (SMAD4) genes can cause GS, CS/BRRS, and JPS, respectively.
Aims-To examine the contribution of mutations in PTCH, PTEN, and DPC4 (SMAD
4) to JPS.
Methods-Forty seven individuals from 15 families and nine apparently sporad
ic cases with JPS were screened for germline mutations in DPC4, PTEN, and P
Results-No patient had a mutation in PTEN or PTCH. Five different germline
mutations were detected in DPC4; three of these were deletions, one a singl
e base substitution creating a stop codon, and one a missense change. None
of these patients had distinguishing clinical features.
Conclusions-Mutations in PTEN and PTCH are unlikely to cause juvenile polyp
osis in the absence of clinical features indicative of CS, ERRS, or GS, A p
roportion of JPS patients harbour DPC4 mutations (21% in this study) but th
ere remains uncharacterised genetic heterogeneity in JPS.