Related Experiment Video
Updated: May 12, 2026
Generation of Genomic Deletions in Mammalian Cell Lines via CRISPR/Cas9
Published on: January 3, 2015
Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis
W A van Hattem1, L A A Brosens, W W J de Leng
1Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Large genomic deletions in SMAD4, BMPR1A, and PTEN are a common cause of juvenile polyposis syndrome (JPS). Multiplex ligation-dependent probe amplification (MLPA) is a valuable tool for diagnosing JPS, identifying 14.8% of mutations.
Area of Science:
- Genetics
- Oncology
- Gastroenterology
Background:
- Juvenile polyposis syndrome (JPS) is a rare genetic disorder linked to increased colorectal cancer risk.
- Germline mutations in SMAD4, BMPR1A, ENG, and PTEN are associated with JPS.
- Current genetic testing identifies mutations in only 30-40% of JPS patients.
Purpose of the Study:
- To investigate the role of large genomic deletions in JPS.
- To perform comprehensive genetic analysis of known JPS-associated genes (SMAD4, BMPR1A, PTEN, ENG).
- To evaluate the utility of multiplex ligation-dependent probe amplification (MLPA) in JPS diagnosis.
Main Methods:
- Genetic analysis of 29 JPS patients from 27 families.
- Direct sequencing and MLPA were used to detect germline defects in SMAD4, BMPR1A, PTEN, and ENG.
Main Results:
- Germline defects in SMAD4, BMPR1A, or PTEN were identified in 48.1% of JPS patients.
- Direct sequencing detected 33.3% of mutations, while MLPA identified an additional 14.8% involving large genomic deletions.
- No mutations were found in the ENG gene.
Conclusions:
- Large genomic deletions in SMAD4, BMPR1A, and PTEN are a significant cause of JPS.
- MLPA is effective in detecting these deletions, improving JPS diagnostic yield.
- MLPA is a valuable adjunct to direct sequencing for comprehensive JPS genetic testing.
Background/Aims:
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterised by multiple gastrointestinal juvenile polyps and an increased risk of colorectal cancer. This syndrome is caused by germline mutation of either SMAD4 or BMPR1A, and possibly ENG. PTEN, originally linked to Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, has also been associated with JPS. By direct sequencing, germline mutations are found in only 30-40% of patients with a JPS phenotype. Therefore, alternative ways of inactivation of the known JPS genes, or additional genes predisposing to JPS may be involved. In this study, a comprehensive genetic analysis of SMAD4, BMPR1A, PTEN and ENG is performed through direct sequencing and multiplex ligation-dependent probe amplification (MLPA) in JPS patients.
Methods:
Archival material of 29 patients with JPS from 27 families was collected. Direct sequencing and MLPA analysis were performed to search for germline defects in SMAD4, BMPR1A, PTEN and ENG.
Results:
A germline defect in SMAD4, BMPR1A or PTEN was found in 13 of 27 (48.1%) unrelated JPS patients. Nine mutations (33.3%) were detected by direct sequencing, including six (22.2%) SMAD4 mutations and three (11.1%) BMPR1A mutations. MLPA identified four additional patients (14.8%) with germline hemizygous large genomic deletions, including one deletion of SMAD4, one deletion of exons 10 and 11 of BMPR1A, and two unrelated patients with deletion of both BMPR1A and PTEN. No ENG gene mutations were found.
Conclusion:
Large genomic deletions of SMAD4, BMPR1A and PTEN are a common cause of JPS. Using direct sequencing and MLPA, a germline defect was detected in 48.1% of JPS patients. MLPA identified 14.8% (4/27) of these mutations. Since a substantial percentage of JPS patients carry a germline deletion and MLPA is a reliable and user-friendly technique, it is concluded that MLPA is a valuable adjunct in JPS diagnosis.
More Related Videos
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
05:58Digital Polymerase Chain Reaction Assay for the Genetic Variation in a Sporadic Familial Adenomatous Polyposis Patient Using the Chip-in-a-tube Format
Published on: August 20, 2018
Related Concept Videos
01:33Pleiotropy
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...