Novel EPHB4 mutation in capillary malformation-arteriovenous malformation syndrome 2 (CM-AVM2): the first genetic study in Asians

Abstract Capillary malformation-arteriovenous malformation syndrome (CM-AVM), a rare vascular malformation, is autosomal dominant and characterized by hereditary capillary malformations (CMs) and potential fast-flow vascular malformation underlying CMs in around one-third of patients, affecting approximately 0.3-0.5% of newborns. CM-AVM was first discovered in association with germline RASA-1 mutation and termed CM-AVM type 1 in 2003. Later, germline EPHB4 mutations were detected in RASA-1-negative CM-AVMs, also known as CM-AVM type 2. Although there have been recent genetic studies confirming the molecular basis of CM-AVM, few have focused on Asian populations, leading to the lack of comprehensive molecular profiling. In this study, we report a female patient diagnosed as CM-AVM2 with a novel stop-gain mutation causing loss of function of the EPHB4 gene. As far as we know, this is the first genetic report of germline EPHB4 loss-of-functional mutation related CM-AVM 2 in Asians, extending our understanding of CM-AVM.