Evidence for the founder effect of a novel ACVRL1 splice-site mutation in Hungarian hereditary hemorrhagic telangiectasia families.

Fig. 1. Pedigree of HHT families sharing the ACVRL1 c.625+1 G>C mutation. (a) The correspondent haplotype of all 14 HHT patients at the affected chromosome region. (b) The pedigree of the five families exhibiting the common ancestor. Probands are marked with arrows. Blackened individuals are affected, either by carrying the mutation and/or having definite HHT. In the upper left index †, definite HHT; *, deceased or unavailable patient with epistaxis and telangiectases by hearsay; #, individual presumably affected by the inheritance of HHT. In the upper right index M, ACVRL1 c.625+1 G>C mutation; w, ACVRL1 wild type; u, patient unavailable for genetic screening. Grey symbols represent equivocal HHT status. In Eger, Hungary, recruitment of HHT patients living in our institution’s attendance area (population of 407.000) was started in 2012. Patient recruitment and investigation are described in Appendix S1, Supporting information. So far, we found four different ENG mutations in five families, whereas, only one, yet unpublished, ACVRL1 mutation was observed in five apparently unrelated families. Arguments supporting a possible founder effect of the latter mutation are discussed.