Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia.
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.
Fontalba
Ana
A
Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, Madrid 28040, Spain. afontalba@humv.es
Fernandez-L
Africa
A
García-Alegria
Eva
E
Albiñana
Virginia
V
Garrido-Martin
Eva M
EM
Blanco
Francisco J
FJ
Zarrabeitia
Roberto
R
Perez-Molino
Alfonso
A
Bernabeu-Herrero
Maria E
ME
Ojeda
Maria-Luisa
ML
Fernandez-Luna
Jose L
JL
Bernabeu
Carmelo
C
Botella
Luisa M
LM
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*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II