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A novel BMPR1A mutation affects mRNA splicing in juvenile polyposis syndrome. BACKGROUND: Juvenile polyposis syndrome (JPS) is one of the hereditary polyposis syndromes caused by abnormal regulation of TGF-β signaling because of mutations in BMPR1A and SMAD4. JPS patients with SMAD4 mutations develop cardiovascular events, whereas those with BMPR1A usually do not. Analysis of genetic mutations in JPS patients can be helpful in devising suitable strategies for medical management. In this study, we demonstrate the pathogenicity of a novel intronic mutation in BMPR1A using mRNA extracted from colonic mucosa of a boy with JPS. METHODS: Genomic DNA extracted from peripheral blood and total RNA isolated from the colonic mucosa were used for DNA sequencing and RT-PCR analyses, respectively. RESULTS: A 13-year-old boy, with no previous medical history, presented to the hospital complaining of bloody stools. Colonoscopy revealed multiple polyps in the colon, and the resected polyps were compatible with juvenile polyps. Sequencing analysis revealed a novel intronic mutation (c.778+5G>C) in BMPR1A. RT-PCR analysis of RNA extracted from the colonic mucosa showed an aberrant splicing form of BMPR1A. Trio analysis showed that his mother also had the same BMPR1A mutation. She was diagnosed with cancer of the cecum and polyposis of the colon at the age of 41. CONCLUSION: We demonstrate the presence of a novel BMPR1A intronic mutation that exhibits splicing abnormality in a family with JPS. Further research and development will help elucidate the genotype-phenotype relationship in JPS.