Type 1 von Willebrand Disease in a Pediatric Patient Caused by a Novel Heterozygous Deletion of Exons 1 to 6 of the von Willebrand Factor Gene: A Case Report

• Published in: Laboratory medicine 2023-07, Vol.54 (4), p.434-438
• Main Authors: Lapić, Ivana, Radić Antolic, Margareta, Rogić, Dunja, Dejanović Bekić, Sara, Coen Herak, Désirée, Bilić, Ernest, Zadro, Renata
• Format: Article
• Language: English
• Subjects: Child; Exons - genetics; Hemorrhage; Humans; Male; von Willebrand Disease, Type 1 - complications; von Willebrand Disease, Type 1 - diagnosis; von Willebrand Disease, Type 1 - genetics; von Willebrand Diseases - complications; von Willebrand Diseases - diagnosis; von Willebrand Diseases - genetics; von Willebrand Factor - analysis; von Willebrand Factor - genetics
• ISSN: 0007-5027; 1943-7730
• DOI: 10.1093/labmed/lmac138

Abstract A 6-year-old boy was referred to a hematologist due to excessive mucocutaneous bleeding. Diagnostic assessment for von Willebrand disease (VWD) was indicated and included both coagulation and genetic testing. Laboratory testing revealed proportionally decreased von Willebrand factor (VWF) glycoprotein Ib-binding activity (23.6%) compared to VWF antigen (24.7%), similarly decreased VWF collagen-binding activity (24.2%), and normally distributed VWF multimers, with decreased intensity of all fractions. Diagnosis of type 1 VWD was established. Genetic analysis by means of next-generation sequencing (NGS) of VWF and coagulation factor VIII genes did not identify any causative mutations. Additionally, multiplex ligation-dependent probe amplification (MLPA) of VWF gene exons revealed a heterozygous deletion of exons 1 to 6, which is reported in type 1 VWD for the first time. Application of MLPA was crucial for revealing the genetic basis of type 1 VWD in this case, which would have remained undetected if only NGS was used.