title: Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.
abstract: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent hemorrhage from the sites of vascular lesions. Two genes have been identified for HHT. Endoglin, a TGF-beta binding protein which maps to chromosome 9q3, is the gene for HHT1. The type and location of most of the previously described mutations in the endoglin (ENG) gene suggested a dominant-negative model of receptor-complex dysfunction for the molecular basis of this disorder. In this article we describe 11 novel ENG mutations in HHT kindreds, which include missense and splice-site mutations. Two identical missense mutations in unrelated families disrupt the start codon of the gene. In addition, some frameshift and nonsense mutations lead to very low or undetectable levels of transcript from the mutant allele. These combined data suggest that the nature of most ENG mutations is to create a null (nonfunctional) allele, and that there is no requirement for the synthesis of a truncated endoglin protein in the pathogenesis of HHT.
authors.affiliation: Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Gallione
authors.forename: D J
authors.initials: DJ
authors.lastname: Klaus
authors.forename: E Y
authors.initials: EY
authors.lastname: Yeh
authors.forename: T T
authors.initials: TT
authors.lastname: Stenzel
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.forename: K B
authors.initials: KB
authors.lastname: Anthony
authors.forename: K A
authors.initials: KA
authors.lastname: McAllister
authors.forename: M A
authors.initials: MA
authors.lastname: Baldwin
authors.forename: J N
authors.initials: JN
authors.lastname: Berg
authors.forename: A
authors.initials: A
authors.lastname: Lux
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.forename: C P
authors.initials: CP
authors.lastname: Vary
authors.forename: W J
authors.initials: WJ
authors.lastname: Craigen
authors.forename: C J
authors.initials: CJ
authors.lastname: Westermann
authors.forename: M L
authors.initials: ML
authors.lastname: Warner
authors.forename: Y E
authors.initials: YE
authors.lastname: Miller
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: A E
authors.initials: AE
authors.lastname: Guttmacher
authors.forename: D A
authors.initials: DA
authors.lastname: Marchuk
mesh_terms: D000483:Alleles; D015703:Antigens, CD; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D000071063:Endoglin; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000209:etiology / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1