title: Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia.
abstract: BACKGROUND
  Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.
  
  
  METHODS
  Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.
  
  
  RESULTS
  We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.
  
  
  CONCLUSIONS
  Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.
authors.affiliation: Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, Madrid 28040, Spain. afontalba@humv.es
authors.forename: Ana
authors.initials: A
authors.lastname: Fontalba
authors.forename: Africa
authors.initials: A
authors.lastname: Fernandez-L
authors.forename: Eva
authors.initials: E
authors.lastname: García-Alegria
authors.forename: Virginia
authors.initials: V
authors.lastname: Albiñana
authors.forename: Eva M
authors.initials: EM
authors.lastname: Garrido-Martin
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Roberto
authors.initials: R
authors.lastname: Zarrabeitia
authors.forename: Alfonso
authors.initials: A
authors.lastname: Perez-Molino
authors.forename: Maria E
authors.initials: ME
authors.lastname: Bernabeu-Herrero
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Ojeda
authors.forename: Jose L
authors.initials: JL
authors.lastname: Fernandez-Luna
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Botella
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics*; D000071063:Endoglin; D005091:Exons; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*; D013030:Spain; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II