High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome
- 23 August 2007
- journal article
- research article
- Published by BMJ in Journal of Medical Genetics
- Vol. 44 (11), 702-709
- https://doi.org/10.1136/jmg.2007.052506
Abstract
Background: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. Methods: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. Results: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (pSMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (pSMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). Conclusions: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.Keywords
This publication has 33 references indexed in Scilit:
- Chronische Anämie bei hereditärer hämorrhagischer Teleangiektasie und juveniler Polyposis des MagensDeutsche Medizinische Wochenschrift (1946), 2006
- Contiguous Gene Deletion within Chromosome Arm 10q Is Associated with Juvenile Polyposis of Infancy, Reflecting Cooperation between the BMPR1A and PTEN Tumor-Suppressor GenesAmerican Journal of Human Genetics, 2006
- A review of Juvenile Polyposis SyndromeJournal of Gastroenterology and Hepatology, 2005
- Vessels' morphology in SMAD4 and BMPR1A‐related juvenile polyposisAmerican Journal of Medical Genetics Part A, 2005
- Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of functionJournal of Medical Genetics, 2005
- Cronkhite-Canada Syndrome Containing Colon Cancer and Serrated Adenoma LesionsDigestion, 2004
- Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriersHuman Genetics, 2002
- Novel de novo mutation of MADH4/SMAD4 in a patient with juvenile polyposisAmerican Journal of Medical Genetics, 2002
- Variant Manifestation of Cowden Disease in Japan: Hamartomatous Polyposis of the Digestive Tract with Mutation of the PTEN GeneAmerican Journal of Human Genetics, 1999
- Molecular Classification of the Inherited Hamartoma Polyposis Syndromes: Clearing the Muddied WatersAmerican Journal of Human Genetics, 1998