RESUMEN
OBJECTIVE: To analyze clinical features of 4 families with hereditary hemorrhagic telangiectasia (HHT) and potential mutations of ENG, ACVRL1 and SMAD4 genes. METHODS: Four unrelated HHT patients and their affected family members were analyzed. All exons and flanking regions of ENG, ACVRL1 and SMAD4 genes were analyzed with PCR and direct sequencing and multiplex ligation-dependent probe amplification (MLPA) methods. RESULTS: Eleven patients from the 4 families were enrolled in this study. Two ENG and 1 ACVRL1 mutations were identified, among which an ENG mutation (c.207G>A; p.L69L) and an ACVRL1 mutation (c.817C>T; p.L273L) have been previously reported. In addition, a novel ENG mutation (c.1004A>T; p.Q335L) has been found in 3 different families. Similar mutations were not detected in 200 healthy individuals. No mutations of ENG, ACVRL1 and SMAD4 were found in the fourth family. CONCLUSION: A novel mutation c.1004A>T (p. Q335L) of ENG has been identified in patients with HHT. And there is significant phenotypic variability and genetic heterogeneity with the disease.