Whole genome sequencing and disease pattern in patients with juvenile polyposis syndrome: a nationwide study

AbstractJuvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected inSMAD4 orBMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant inBMPR1A orSMAD4. In patients where no variant had been detected, we performed genetic analysis, including whole genome sequencing. We collected clinical information on all patients to investigate the phenotypic spectrum. Sixty-six patients (mean age 40  years) were included of whom the pathogenic variant was unknown in seven patients. We detected a pathogenic variant inSMAD4 orPTEN in additional three patients and thus ≈ 95% of patients had a pathogenic germline variant. Endoscopic information was available in fifty-two patients (79%) and of these 31 (60%) fulfilled the clinical criteria of JPS. In 41 patients (79%), other types of polyps than juvenile had been removed. Our results suggest that almost all patie nts with a clinical diagnosis of JPS has a pathogenic variant in mainlyBMPR1A,SMAD4, and more rarelyPTEN. However, not all patients with a pathogenic variant fulfil the clinical criteria of JPS. We also demonstrated a wide clinical spectrum, and that the histopathology of removed pol...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research