title: Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients.
abstract: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant disorder characterized by an aberrant vascular development. The resulting vascular lesions range from smaller mucocutaneous telangiectases to large visceral arteriovenous malformations, especially in the skin, lung, gastrointestinal tract and the brain. Mutations in the genes encoding endoglin (ENG, chromosome 9q34) and activin A receptor type-like kinase 1 (ALK-1, also named ACVRL1, chromosome 12q13) are associated with HHT1 and HHT2, respectively. We report here on the genetic and molecular heterogeneity found in the HHT population in the Netherlands. Probands of 104 apparently unrelated families were studied and we performed sequence analysis on both the ENG gene and ALK-1 gene. In most of the probands, we found a mutation in one of the two genes: 53% in the ENG gene and 40% in the ALK-1 gene. In 7% of the families no ENG or ALK1 mutation was found. The mutations detected were deletions, insertions, nonsense, missense and splice site mutations. The majority were novel mutations.
authors.affiliation: DBG-Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands. T.G.W.Letteboer@dmg.azu.nl
authors.forename: T G W
authors.initials: TG
authors.lastname: Letteboer
authors.forename: R A
authors.initials: RA
authors.lastname: Zewald
authors.forename: E J
authors.initials: EJ
authors.lastname: Kamping
authors.forename: G
authors.initials: G
authors.lastname: de Haas
authors.forename: J J
authors.initials: JJ
authors.lastname: Mager
authors.forename: R J
authors.initials: RJ
authors.lastname: Snijder
authors.forename: D
authors.initials: D
authors.lastname: Lindhout
authors.forename: F A M
authors.initials: FA
authors.lastname: Hennekam
authors.forename: C J J
authors.initials: CJ
authors.lastname: Westermann
authors.forename: J K
authors.initials: JK
authors.lastname: Ploos van Amstel
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D030301:Activin Receptors, Type II; D000595:Amino Acid Sequence; D015703:Antigens, CD; D004252:DNA Mutational Analysis; D000071063:Endoglin; D006801:Humans; D008969:Molecular Sequence Data; D009426:Netherlands; D011956:Receptors, Cell Surface; D016415:Sequence Alignment; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II