The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis
- 31 December 2008
- journal article
- Published by Wiley in Clinical Genetics
- Vol. 75 (1), 79-85
- https://doi.org/10.1111/j.1399-0004.2008.01091.x
Abstract
Juvenile polyposis (JPS) is an autosomal dominant syndrome that predisposes individuals to develop gastrointestinal polyps and cancer. Germline point mutations in SMAD4 and BMPR1A have been identified as causing JPS in approximately 40–60% of patients, but few studies have looked at the rate of large deletions. In this study, we determined the overall prevalence of genetic changes of SMAD4 and BMPR1A by sequencing and by screening for larger deletions. DNA was extracted from 102 JPS probands, and each exon and intron–exon boundary of SMAD4 and BMPR1A were sequenced. Coding and non‐coding exons of SMAD4 and BMPR1A were screened for deletions with multiplex ligation‐dependent probe amplification (MLPA). By sequencing, 20 probands had point mutations of SMAD4 and 22 of BMPR1A. By MLPA, one proband had deletion of most of SMAD4, one of both BMPR1A and PTEN, one of the 5′ end of BMPR1A, and another of the 5′ end of SMAD4. The overall prevalence of SMAD4 and BMPR1A point mutations and deletions in JPS was 45% in the largest series of patients to date. Large deletions are less frequent in JPS patients, but represent other heritable causes of JPS, which should be screened for in pre‐symptomatic genetic testing.Keywords
This publication has 32 references indexed in Scilit:
- Risk of colorectal cancer in juvenile polyposisGut, 2007
- Vessels' morphology in SMAD4 and BMPR1A‐related juvenile polyposisAmerican Journal of Medical Genetics Part A, 2005
- Gastric juvenile polyposis associated with germline SMAD4 mutationAmerican Journal of Medical Genetics Part A, 2005
- Comprehensive Analysis of SMAD4 Mutations and Protein Expression in Juvenile PolyposisThe American Journal of Pathology, 2001
- Frequent 4-bp deletion in exon 9 of theSMAD4/MADH4 gene in familial juvenile polyposis patientsGenes, Chromosomes and Cancer, 1999
- Mutations in the SMAD4/DPC4 Gene in Juvenile PolyposisScience, 1998
- A Gene for Familial Juvenile Polyposis Maps to Chromosome 18q21.1American Journal of Human Genetics, 1998
- Malignant potential in intestinal juvenile polyposis syndromesAnnals of Surgical Oncology, 1995
- Colorectal neoplasia in juvenile polyposis or juvenile polyps.Archives of Disease in Childhood, 1991
- Pathology of Polyposis Syndromes with Special Reference to Juvenile PolyposisPublished by Springer Science and Business Media LLC ,1990