BMP9 Mutations Cause a Vascular-Anomaly Syndrome with Phenotypic Overlap with Hereditary Hemorrhagic Telangiectasia
| العنوان: | BMP9 Mutations Cause a Vascular-Anomaly Syndrome with Phenotypic Overlap with Hereditary Hemorrhagic Telangiectasia |
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| المؤلفون: | Beth L. Roman, James R. Runo, Gyula T. Fülöp, Whitney Wooderchak-Donahue, Sarah Young, Brendan D. O'Fallon, Parker Plant, Nicholas W. Morrell, David A. Stevenson, Wei Li, Jamie McDonald, Paul D. Upton, Carmen Langa, Pinar Bayrak-Toydemir, Carmelo Bernabeu, Luisa María Botella |
| المساهمون: | National Institutes of Health (US), British Heart Foundation, Ministerio de Economía y Competitividad (España), Wooderchak-Donahue, Whitney [0000-0002-9358-7466], O'Fallon, Brendan D. [0000-0001-7185-7894], Roman, Beth L. [0000-0002-1250-1705], Young, Sarah [0000-0002-8301-5106], Morrell, Nicholas W. [0000-0001-5700-9792], Botella, Luisa María [0000-0002-6310-2245], Bernabéu, Carmelo [0000-0002-1563-6162], Bayrak-Toydemir, Pinar [0000-0001-9381-2478], Wooderchak-Donahue, Whitney, O'Fallon, Brendan D., Roman, Beth L., Young, Sarah, Morrell, Nicholas W., Botella, Luisa María, Bernabéu, Carmelo, Bayrak-Toydemir, Pinar |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | The American Society of Human Genetics. Published by Elsevier Inc. |
| مصطلحات موضوعية: | Proband, Male, Identification, Telangiectases, Ligands, Rasa1 mutations, Capillary, Mice, 0302 clinical medicine, Transforming Growth Factor beta, Receptors, Endothelial-cells, Growth Differentiation Factor 2, Genetics(clinical), Weber-syndrome, Exome, Genetics (clinical), Zebrafish, Genetics, Sanger sequencing, 0303 health sciences, Syndrome, Phenotype, 3. Good health, Growth Differentiation Factors, symbols, Female, Telangiectasia, Hereditary Hemorrhagic, Protein Binding, Signal Transduction, Adult, Adolescent, Locus, Mutation, Missense, GDF2, Biology, Vascular anomaly, Arteriovenous malformation, 03 medical and health sciences, symbols.namesake, Report, medicine, Animals, Humans, Genetic Predisposition to Disease, 030304 developmental biology, ACVRL1, medicine.disease, Amino Acid Substitution, Kinase 1 alk1, Mutation, Blood Vessels, Protein Processing, Post-Translational, 030217 neurology & neurosurgery |
| الوصف: | 8 p.-5 fig.-1 tab. Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is caused by mutations in genes involved in the transforming growth factor beta (TGF-β) signaling pathway (ENG, ACVRL1, and SMAD4). Yet, approximately 15% of individuals with clinical features of HHT do not have mutations in these genes, suggesting that there are undiscovered mutations in other genes for HHT and possibly vascular disorders with overlapping phenotypes. The genetic etiology for 191 unrelated individuals clinically suspected to have HHT was investigated with the use of exome and Sanger sequencing; these individuals had no mutations in ENG, ACVRL1, and SMAD4. Mutations in BMP9 (also known as GDF2) were identified in three unrelated probands. These three individuals had epistaxis and dermal lesions that were described as telangiectases but whose location and appearance resembled lesions described in some individuals with RASA1-related disorders (capillary malformation-arteriovenous malformation syndrome). Analyses of the variant proteins suggested that mutations negatively affect protein processing and/or function, and a bmp9-deficient zebrafish model demonstrated that BMP9 is involved in angiogenesis. These data confirm a genetic cause of a vascular-anomaly syndrome that has phenotypic overlap with HHT. This work was funded by the Associated Regional and University Pathologists Institute for Clinical and Experimental Pathology, a National Institutes of Health grant R01 (HL079108 to B.L.R.), a British Heart Foundation Programme grant (RG/08/002/24718 to N.W.M), and the Ministerio de Economia y Competitividad of Spain (SAF2010-19222 to C.B.). |
| اللغة: | English |
| تدمد: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2013.07.004 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ac3cd488d62ac2cf9b4c97b0a64abb6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6ac3cd488d62ac2cf9b4c97b0a64abb6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029297 |
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| DOI: | 10.1016/j.ajhg.2013.07.004 |