ALK-1 Gene Mutation in a Chinese Family with HHT

Hereditary Hemorrhagic Telangiectasia (HTT) is an autosomal dominant bleeding disorder characterized by localized angiodysplasia.Recent studies demonstrated mutations in the activin receptor-like kinase-1(ALK-1) and endoglin (ENG)gene in patienets with HHT except from China. Objectives: The aim of this study is to identify the mutation of ENG and ALK-1 genes of a Chinese family with HHT. Methods: 13 members from the family with 6 affected individuals(One of whom attended our clinic with recurrent tongue-bleed) were included in this study. Extrons of endoglin and ALK-1 genes were amplified using primers designed by Primer 3 software and PCR products were sequenced directly using T7 sequencing system. The results were analyzed by BioEdit. Results: one novel mutation were detected in extron 10 of ALK-1gene--- a substitution mutation C13399T in all 6 symptomatic family members(which has not been identified previously), but the mutation was absent in the 7 healthy members of the family. The mutation leads CGA(Arginine R) into TGA(termination condon*, R479*)(result in/from mutate protein). No mutations in the endoglin locus were found. Conclusions: These results suggest that ALK-1 gene mutation is related to the disease state of this HHT Chinese family and a presympomatic screening program for HHT would feasible.