title: Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.
abstract: Hereditary haemorrhagic telangiectasia (HHT) is a rare disorder with one per 6000-10,000 affected individuals in the general Caucasian population. HHT is genetically heterogeneous, involving at least two loci HHT1 mapping to chromosome 9q34.1 and HHT2 mapping to chromosome 12q31. The loci have been identified as endoglin (ENG) and activin receptor-like kinase 1 (ALK1). In order to gain knowledge of the genotype distribution and prevalence in the Danish population and to establish a reproducible and sensitive molecular genetic test method, we developed a denaturating gradient gel electrophoresis protocol for mutation scanning of the two loci. Twenty-five Danish HHT families were tested. A total of eight new as well as seven previously reported mutations were identified. A founder mutation was characterized present in seven families and possibly introduced around 350 years ago. In one individual, a presumed spontaneous mutation was characterized. The method developed proved to be very sensitive for mutation detection in both ENG and ALK1. Genetic screening in HHT families facilitates an early treatment strategy for silent HHT manifestations in first degree relatives.
authors.affiliation: Department of Clinical Biochemistry and Molecular Genetics, Odense University Hospital, Odense C, Denmark. klaus.brusgaard@ouh.fyns-amt.dk
authors.forename: K
authors.initials: K
authors.lastname: Brusgaard
authors.forename: A D
authors.initials: AD
authors.lastname: Kjeldsen
authors.forename: L
authors.initials: L
authors.lastname: Poulsen
authors.forename: H
authors.initials: H
authors.lastname: Moss
authors.forename: P
authors.initials: P
authors.lastname: Vase
authors.forename: K
authors.initials: K
authors.lastname: Rasmussen
authors.forename: T A
authors.initials: TA
authors.lastname: Kruse
authors.forename: M
authors.initials: M
authors.lastname: Hørder
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D015703:Antigens, CD; D002881:Chromosomes, Human, Pair 12; D002899:Chromosomes, Human, Pair 9; D004252:DNA Mutational Analysis; D003718:Denmark; D004586:Electrophoresis; D000071063:Endoglin; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011956:Receptors, Cell Surface; 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; D030201:Activin Receptors, Type I