Analysis of genetic and phenotypic heterogeneity in juvenile polyposis

Citation
K. Woodford-richens et al., Analysis of genetic and phenotypic heterogeneity in juvenile polyposis, GUT, 46(5), 2000, pp. 656-660
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
GUT
ISSN journal
0017-5749 → ACNP
Volume
46
Issue
5
Year of publication
2000
Pages
656 - 660
Database
ISI
SICI code
0017-5749(200005)46:5<656:AOGAPH>2.0.ZU;2-P
Abstract
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 TCH. 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.