Patients and mutation analysis
In this study, the underlying patho-molecular mechanisms VWFpp variants detected in six index patients (IPs) from Germany and Pakistan. The VWD diagnosis and classification of the IPs were made based on bleeding symptoms and standard coagulation tests, consistent with ISTH-SSC VWF guidelines. The VWF analysis was before performed in Bonn Haemophilia Center, and the result of the genetic analysis, as well as coagulation tests, has been previously reported . DNA and protein sequence numbering has been done based on the reference sequence: RefSeq NM_000552.4 and NP_000543.2, respectively, and sequence variant descriptions were verified by VariantValidator online tool (https://variantvalidator.org/; accessed on 20.09.2020). The investigated VWF variants have been registered to the Leiden Open Variation Database (LOVD version 3.0;http://www.lovd.nl/3.0/home; submission individuals IDs: 00311186‐ 00311190 as well as 00311192).