Chinese capillary malformation-arteriovenous malformation: clinical and genetic analysis of eight cases

Background Capillary malformation-arteriovenous malformation (CM-AVM) is an inherited autosomal dominant vascular disorder associated with RAS p21 protein activator ( RASA1 ) or EPH receptor B4 ( EPHB4 ) mutations. We aimed to investigate the clinical features of eight Chinese families with CM-AVM and the genetic characteristics of EPHB4 or RASA1 gene variants. Methods The clinical data of eight families with CM-AVM who were admitted to the Department of Dermatology, the Union Affiliated Hospital of Fujian Medical University from January 2022 to September 2023 were collected and analyzed. Whole-Exome Sequencing was used to detect the pathogenic gene in the probands, and Sanger sequencing was used to verify the gene mutation sites in family members. Homology modeling software was used to predict the three-dimensional structure of the protein and analyze the characteristics of gene mutations. Results Five EPHB4 gene variants and two RASA1 mutations were detected in eight patients. Five of these were novel variations: four EPHB4 (c.2197G>T, p.E733X; c.2451_2460delGGAGAGGCCG, p.E818Tfs * 4; c.1899_1900insTTGGCGAGGTGTGTCGGGGGCGG, p.K635Afs * 23; c.2018A>G, p.H673R) and one RASA1 (c.1848T>A, p.C616X). There were two missense mutations, two frameshift mutations and one non-sense mutation in EPHB4 mutation, and two non-sense mutations in RASA1 mutation. Conclusions The clinical characteristics of CM-AVM include multifocal capillary malformations (CMs), telangiectasia, and arteriovenous malformation (AVM) or arteriovenous fistulas (AVF). The novel mutations could expand the spectrum of CM-AVM associated with EPHB4 or RASA1 mutations.