Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis

• DOI: 10.1136/gut.2007.142927
• Publication Date: 2008-01-05T01:44:52Z
• Authors: W. A. van Hattem; L. A. A. Brosens; W. W. J. de Leng; F. H. Morsink; S. Lens; R. Carvalho; F. M. Giardiello; G. J. A. Offerhaus
• Keywords: Cowden syndrome; Germline mosaicism

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterised by multiple gastrointestinal juvenile polyps and an increased risk of colorectal cancer. This caused germline mutation either SMAD4 or BMPR1A, possibly ENG. PTEN, originally linked to Cowden Bannayan-Riley-Ruvalcaba syndrome, has also been associated with JPS. By direct sequencing, mutations are found in only 30-40% patients JPS phenotype. Therefore, alternative ways inactivation the known genes, additional genes predisposing may be involved. In this study, comprehensive genetic analysis SMAD4, PTEN ENG performed through sequencing multiplex ligation-dependent probe amplification (MLPA) patients.Archival material 29 from 27 families was collected. Direct MLPA were search for defects ENG.A defect BMPR1A 13 (48.1%) unrelated patients. Nine (33.3%) detected including six (22.2%) three (11.1%) mutations. identified four (14.8%) hemizygous large genomic deletions, one deletion exons 10 11 two both PTEN. No gene found.Large deletions common cause Using MLPA, 48.1% 14.8% (4/27) these Since substantial percentage carry reliable user-friendly technique, it concluded that valuable adjunct diagnosis.