Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis colorectal cancer in the same kindred.

Endoglin (CD105) is a proliferation-associated protein that is strongly expressed in endothelial tissue and has a role in tumor angiogenesis. Mutations in endoglin are also linked to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disease associated with aberrant angiogenesis. We report an unusual association of HHT1 and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) in the same kindred. Genetic analysis indicates that these 2 syndromes are genetically unrelated and separately segregated within the family. The mutation in the endoglin gene leads to a truncated protein. The mutation in the mismatch repair gene MLH1 causes a splicing defect, giving synthesis to an unstable mRNA from this mutated allele. The potential protective role of an endoglin mutation in patients with HNPCC is discussed.