A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disorder of vascular development. Common manifestations include epistaxis, telangiectasias and arteriovenous malformations in multiple organs. Different deletions or nonsense mutations have been described in the ENG (HHT1) or ACVRL1/ALK1 (HHT2) g...
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MDPI AG
2022-05-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/11/3053 |
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| author | Suriel Errasti Díaz Mercedes Peñalva Lucía Recio-Poveda Susana Vilches Juan Casado-Vela Julián Pérez Pérez Luisa María Botella Virginia Albiñana Angel M. Cuesta |
| author_facet | Suriel Errasti Díaz Mercedes Peñalva Lucía Recio-Poveda Susana Vilches Juan Casado-Vela Julián Pérez Pérez Luisa María Botella Virginia Albiñana Angel M. Cuesta |
| author_sort | Suriel Errasti Díaz |
| collection | DOAJ |
| description | Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disorder of vascular development. Common manifestations include epistaxis, telangiectasias and arteriovenous malformations in multiple organs. Different deletions or nonsense mutations have been described in the ENG (HHT1) or ACVRL1/ALK1 (HHT2) genes, all affecting endothelial homeostasis. A novel mutation in <i>ACVRL1/ALK1</i> has been identified in a Peruvian family with a clinical history compatible to HHT. Subsequently, 23 DNA samples from oral exchanges (buccal swaps) of the immediate family members were analyzed together with their clinical histories. A routine cDNA PCR followed by comparative DNA sequencing between the founder and another healthy family member showed the presence of the aforementioned specific mutation. The single mutation detected (c.525 + 1G > T) affects the consensus splice junction immediately after exon 4, provokes anomalous splicing and leads to the inclusion of intron IV between exons 4 and 5 in the <i>ACVRL1/ALK1</i> mRNA and, therefore, to <i>ALK1</i> haploinsufficiency. Complete sequencing determined that 10 of the 25 family members analyzed were affected by the same mutation. Notably, the approach described in this report could be used as a diagnostic technique, easily incorporated in clinical practice in developing countries and easily extrapolated to other patients carrying such a mutation. |
| first_indexed | 2024-03-10T01:11:59Z |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T01:11:59Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-27b6a22881ff4e7c8b5d8e156cbc7ddb2023-11-23T14:16:01ZengMDPI AGJournal of Clinical Medicine2077-03832022-05-011111305310.3390/jcm11113053A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2Suriel Errasti Díaz0Mercedes Peñalva1Lucía Recio-Poveda2Susana Vilches3Juan Casado-Vela4Julián Pérez Pérez5Luisa María Botella6Virginia Albiñana7Angel M. Cuesta8Departamento Hematología, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, PeruDepartamento Biomedicina Molecular, Centro de Investigaciones Biológicas Margarita Salas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), 280406 Madrid, SpainDepartamento Biomedicina Molecular, Centro de Investigaciones Biológicas Margarita Salas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), 280406 Madrid, SpainLaboratorio Diagnóstico Genético Secugen SL, CIB, CSIC, 28040 Madrid, SpainFacultad de Ciencias Experimentales, Universidad Francisco de Vitoria, Pozuelo, 28223 Madrid, SpainLaboratorio Diagnóstico Genético Secugen SL, CIB, CSIC, 28040 Madrid, SpainDepartamento Biomedicina Molecular, Centro de Investigaciones Biológicas Margarita Salas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), 280406 Madrid, SpainDepartamento Biomedicina Molecular, Centro de Investigaciones Biológicas Margarita Salas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), 280406 Madrid, SpainCIBERER, Unidad 707, Instituto de Salud Carlos III (ISCIII), 28029 Madrid, SpainHereditary Hemorrhagic Telangiectasia (HHT) is a rare disorder of vascular development. Common manifestations include epistaxis, telangiectasias and arteriovenous malformations in multiple organs. Different deletions or nonsense mutations have been described in the ENG (HHT1) or ACVRL1/ALK1 (HHT2) genes, all affecting endothelial homeostasis. A novel mutation in <i>ACVRL1/ALK1</i> has been identified in a Peruvian family with a clinical history compatible to HHT. Subsequently, 23 DNA samples from oral exchanges (buccal swaps) of the immediate family members were analyzed together with their clinical histories. A routine cDNA PCR followed by comparative DNA sequencing between the founder and another healthy family member showed the presence of the aforementioned specific mutation. The single mutation detected (c.525 + 1G > T) affects the consensus splice junction immediately after exon 4, provokes anomalous splicing and leads to the inclusion of intron IV between exons 4 and 5 in the <i>ACVRL1/ALK1</i> mRNA and, therefore, to <i>ALK1</i> haploinsufficiency. Complete sequencing determined that 10 of the 25 family members analyzed were affected by the same mutation. Notably, the approach described in this report could be used as a diagnostic technique, easily incorporated in clinical practice in developing countries and easily extrapolated to other patients carrying such a mutation.https://www.mdpi.com/2077-0383/11/11/3053<i>ACVRL1/ALK1</i>hereditary hemorrhagic telangiectasiasplicing mutationOsler-Weber-Rendu disease |
| spellingShingle | Suriel Errasti Díaz Mercedes Peñalva Lucía Recio-Poveda Susana Vilches Juan Casado-Vela Julián Pérez Pérez Luisa María Botella Virginia Albiñana Angel M. Cuesta A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2 Journal of Clinical Medicine <i>ACVRL1/ALK1</i> hereditary hemorrhagic telangiectasia splicing mutation Osler-Weber-Rendu disease |
| title | A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2 |
| title_full | A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2 |
| title_fullStr | A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2 |
| title_full_unstemmed | A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2 |
| title_short | A Novel Splicing Mutation in the <i>ACVRL1/ALK1</i> Gene as a Cause of HHT2 |
| title_sort | novel splicing mutation in the i acvrl1 alk1 i gene as a cause of hht2 |
| topic | <i>ACVRL1/ALK1</i> hereditary hemorrhagic telangiectasia splicing mutation Osler-Weber-Rendu disease |
| url | https://www.mdpi.com/2077-0383/11/11/3053 |
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