title: Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families.
abstract: Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagic telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2. Other distinct phenotype-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995. All living patients and their first-degree relatives were invited to attend a detailed clinical examination and blood was drawn for mutation analysis. In two families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutation no individuals with PAVM were identified and only one patient had a history of severe GI bleeding. No mutations in the endoglin locus were found in either family.
authors.affiliation: Genetic Epidemiologic Research Unit, Odense University, 5000 Odense C, Denmark. jakjeldsen@dadlnet.dk
authors.forename: A D
authors.initials: AD
authors.lastname: Kjeldsen
authors.forename: K
authors.initials: K
authors.lastname: Brusgaard
authors.forename: L
authors.initials: L
authors.lastname: Poulsen
authors.forename: T
authors.initials: T
authors.lastname: Kruse
authors.forename: K
authors.initials: K
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Green
authors.forename: P
authors.initials: P
authors.lastname: Vase
mesh_terms: D029404:Activin Receptors; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003718:Denmark; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics* / Q000473:pathology
chemical_list: D004247:DNA; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors