title: Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis colorectal cancer in the same kindred.
abstract: 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.
authors.affiliation: Department of Medicine, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Goldschmidt
authors.forename: Shulamit
authors.initials: S
authors.lastname: Metzger
authors.forename: Isaiah D
authors.initials: ID
authors.lastname: Wexler
authors.forename: Orit
authors.initials: O
authors.lastname: Goldshmidt
authors.forename: Tiberiu
authors.initials: T
authors.lastname: Hershcovici
authors.forename: Tova
authors.initials: T
authors.lastname: Chajek-Shaul
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair; D000071063:Endoglin; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D002352:Carrier Proteins; C064206:ENG protein, human; D000071063:Endoglin; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D000070957:MutL Protein Homolog 1