TEK C2545T Germline Mutation in Blue Rubber Bleb Nevus Syndrome

Objective: Blue rubber bleb nevus (BRBNS) syndrome is characterized by numerous venous malformations, which usually affect the skin, mucous, and gastrointestinal tract. However, the mechanisms of BRBNS syndrome are unclear. Materials and Methods: Blood samples were obtained from the fivegeneration pedigree and Genomic DNA was extracted from blood samples with a TianGen DNA Extraction Kit. Agilent SureSelect Exon sequencing was applied to capture suspicious mutation sites. The suspected pathogenic gene mutations were amplified with polymerase chain reaction (PCR) and analyzed with Sanger sequencing. Results: In this study, we found a five-generation pedigree with venous malformations that were suspected to be blue rubber bleb nevi. The cosegregation of disease phenotypes indicated the autosomal dominant mutation phenomenon. Heterozygous and inherited TEK mutations for the c.2545C>T substitution were detected in 3 affected members (II2, II14 and IV2), while the unaffected family members (II6 and IV7) carried the wild-type TEK gene, which cosegregated with the phenotype in this pedigree. Therefore, the novel missense variant c.2545C>T enriched the TEK mutation spectrum and may serve as a valuable genetic marker for the molecular diagnosis and prompt genetic counseling for BRBN. Conclusion: This study identified a novel inherited germline C2545T mutation in exon 15 of the TEK gene that can contribute to the pathology of pedigree-based venous malformations.