Registry-Based Frequency of Molecularly Confirmed Osteogenesis Imperfecta in a Swiss Cohort of Individuals With...

Patient registries play a crucial role in advancing our understanding of rare diseases, enabling the collection of comprehensive clinical and molecular data that inform diagnosis, treatment, and management strategies and advance our understanding of rare diseases. We showcase the first Swiss registry of 796 patients with suspected or confirmed connective tissue disorders (CTD) who were referred to our center over a period of 26 years between 1995 and 2022. The registry contains information on the natural history, anthropometrics, biochemical, histological, and genetic analyses. 61.3% of patients were referred by other hospitals or genetic specialists, with the primary reasons for referral being suspicion of Ehlers-Danlos syndrome (EDS) (53.6%) and osteogenesis imperfecta (OI) (28.1%). Molecular confirmation of these diagnoses was obtained in 60 cases of EDS and 98 cases of OI through genetic testing. In-depth analyses of 173 OI patients revealed that the majority of OI cases were caused by mutations in COL1A1 or COL1A2. Rarer variants were identified in genes involved in collagen synthesis and bone regulation. Genotype-phenotype correlations were observed in a small subset of patients, with a high prevalence of glycine substitutions in COL1A1 and COL1A2 variants associated with severe phenotypes. This registry offers insights into the molecular underpinnings of EDS and OI and underscores the importance of genetic testing for accurate diagnosis and management.