BMPR1A and SMAD4 mutations in juvenile polyposis syndrome: clinicopathological and genetic data from two congolese patients

Abstract Background Juvenile polyposis syndrome (JPS) is a rare genetic disorder due to germline mutations in BMPR1A or in SMAD4 that are both tumor suppressor genes. The main clinical manifestation is the presence of multiple hamartomatous polyps preferentially located in gastrointestinal tract, mostly in colorectal site. The polyps can degenerate and lead to inherited malignant tumors. Materials and Methods Among 3157 patients with malignant and benign tumors diagnosed in Brazzaville teaching hospital, 43 persons with polyposis in colorectal tube were recruited. The positive diagnosis was based on endoscopic examination, World Health Organization and JASS guidelines clinical criteria, histopathological analysis and next-generationsequencing of DNAs extracted from peripheral blood of the patients. Results Among 43 patients having polyposis, two were male patients identified with JPS representing 4.65% of polyposis and 0.06% of all tumors. Histological examination revealed typical JPS features. In those two males, whole genome comparative microarray did not identify relevant copy number imbalances. DNA sequencing of a comprehensive gene cancer genes panel identified specific mutations in the BMPR1A and SMAD4 genes. Conclusion We have shown that BMPR1A and SMAD4 gene disorders are responsible for JPS in congolese patients as well and a novel mutation has been identified in one individual. As the condition predisposes highly to hereditary colorectal cancer, a comprehensive assessment of the JPS including genetic testing should be implemented in order to facilitate early diagnosis in Congo Brazzaville.