LAUSR

Introduction/Background Symptomatic joint hypermobiliy has been associated with bleeding tendency, suggesting that collagen disorders could be the cause in some cases of bleeding. The aim of this study was to examine the clinical characteristics of patients with bleeding tendency of unknown cause and joint hypermobility and to perform a genetic study based on Next-Generation Sequencing (NGS). Material and method This was a single-centre, prospective, observational study. Patients included were a Haemophilia Centre (HC) for bleeding symptoms of unknown cause (normal or abnormal haemostatic tests not explaining the bleeding phenotype) and having joint laxity and Musculoskeletical Rehabilitation Unit (RHB) for joint laxity and reporting bleeding symptoms. Bleeding severity was assessed by the haematologist using the ISTH Bleeding assessment tool (ISTHBAT) and joint hyperlaxity by the physiatrist by the Beighton score. Molecular analysis was performed using TruSight One Sequencing Panel Kit (Illumina). Quality and population frequency filters were applied and the search was limited to 78 genes related with Heritable Disorders of Connective Tissue (HDCT). Results Forty-three patients were included between June 2016 and January 207. All were females; median age was 38.6 years (range 17–62 years). Median ISTH-BAT score was 8 (range 3–17) and Beighton score 7 to 9 (range 3–9). ISTH-BAT score was abnormal in 77% and Beighton score in 80%. In 25 patients, both scores were abnormal. A total of 175 potential mutations were identified in HDCT related genes for all except one patient. In 46.5% a direct correlation between the identified mutation and the clinical phenotype could be established. In 10 patients, mutations in COL5A1, COL5A2, COL1A1 and COL1A2 genes were identified and validated by Sanger sequencing. Conclusion Clinical assessment for symptomatic joint hypermobility should be considered in patients with significant bleeding history of unknown cause. NGS could be a useful tool for the study of the responsible genes and the classification of patients.