Copy number variations in endoglin locus: mapping of large deletions in Spanish families with hereditary hemorrhagic telangiectasia type 1

The hereditary hemorrhagic telangiectasia syndrome (HHT), also known as the Rendu-Osler-Weber syndrome is a multiorganic vascular disorder inherited as an autosomal dominant trait. Diagnostic clinical criteria include: epistaxis, telangiectases in mucocutaneous and gastrointestinal sites, arterioven...

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Published in:BMC genetics 2013-11, Vol.14 (1), p.121-121, Article 121
Main Authors: Fontalba, Ana, Fernández-Luna, Jose L, Zarrabeitia, Roberto, Recio-Poveda, Lucia, Albiñana, Virginia, Ojeda-Fernández, Maria L, Bernabéu, Carmelo, Alcaraz, Luis A, Botella, Luisa M
Format: Article
Language:English
Subjects:
Antigens, CD - genetics
Chromosome Mapping
Cyclin-Dependent Kinase 9 - genetics
Deoxyribonucleic acid
DNA
DNA Copy Number Variations
Endoglin
Ethics
European Continental Ancestry Group - genetics
Exons
Gene Deletion
Gene expression
Genetic Association Studies
Genetic Loci
Genetics
Genotype
Hospitals
Humans
Kinases
Ligands
Multiplex Polymerase Chain Reaction
Mutation
Patients
Phenotype
Promoter Regions, Genetic
Receptors, Cell Surface - genetics
Spain
Telangiectasia, Hereditary Hemorrhagic - genetics
Telangiectasia, Hereditary Hemorrhagic - pathology
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Summary:The hereditary hemorrhagic telangiectasia syndrome (HHT), also known as the Rendu-Osler-Weber syndrome is a multiorganic vascular disorder inherited as an autosomal dominant trait. Diagnostic clinical criteria include: epistaxis, telangiectases in mucocutaneous and gastrointestinal sites, arteriovenous malformations (AVMs) most commonly found in pulmonary, hepatic and cerebral circulations, and familial inheritance. HHT is transmitted in 90% of the cases as an autosomal dominant condition due to mutations in either endoglin (ENG), or activin receptor-like kinase 1 (ACVRL1/ALK1) genes (HHT type 1 and 2, respectively). We have carried out a genetic analysis of four independent Spanish families with HHT clinical criteria, which has permitted the identification of new large deletions in ENG. These mutations were first detected using the MLPA technique and subsequently, the deletion breakpoints were mapped using a customized copy number variation (CNV) microarray. The array was designed to cover the ENG gene and surrounding areas. All tested families carried large deletions ranging from 3-kb to 100-kb, involving the ENG gene promoter, several ENG exons, and the two downstream genes FGSH and CDK9. Interestingly, common breakpoints coincident with Alu repetitive sequences were found among these families. The systematic hybridization of DNA from HHT families, with deletions or duplications, to custom designed microarrays, could allow the mapping of breakpoints, coincident with repetitive Alu sequences that might act as "hot spots" in the development of chromosomal anomalies.
ISSN:1471-2350
1471-2156
1471-2350
1471-2156
DOI:10.1186/1471-2350-14-121