A Novel Splicing Mutation in the ACVRL1/ALK1 Gene as a Cause of HHT2

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dc.contributor.authorErrasti Díaz, Suriel
dc.contributor.authorPeñalva, Mercedes
dc.contributor.authorRecio Poveda, Lucía
dc.contributor.authorVilches, Susana
dc.contributor.authorCasado Vela, Juan
dc.contributor.authorPérez Pérez, Julián
dc.contributor.authorBotella, Luisa María
dc.contributor.authorAlbiñana, Virginia
dc.contributor.authorCuesta Martínez, Ángel
dc.date.accessioned2023-06-22T10:49:16Z
dc.date.available2023-06-22T10:49:16Z
dc.date.issued2022-05-28
dc.description.abstractHereditary 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 ACVRL1/ALK1 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 ACVRL1/ALK1 mRNA and, therefore, to ALK1 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.
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Farmacia)
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad (MINECO)
dc.description.sponsorshipMinisterio de Ciencia e Innovación (MICINN)
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/73355
dc.identifier.doi10.3390/jcm11113053
dc.identifier.issn2077-0383
dc.identifier.officialurlhttps://doi.org/10.3390/jcm11113053
dc.identifier.relatedurlhttps://www.mdpi.com/2077-0383/11/11/3053/htm
dc.identifier.urihttps://hdl.handle.net/20.500.14352/71727
dc.issue.number11
dc.journal.titleJournal of Clinical Medicine
dc.language.isoeng
dc.page.initial3053
dc.publisherMPDI
dc.relation.projectIDSAF2017-83351R
dc.relation.projectIDPID2020-115371RB-I00
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordACVRL1/ALK1
dc.subject.keywordhereditary hemorrhagic telangiectasia
dc.subject.keywordsplicing mutation
dc.subject.keywordOsler-Weber-Rendu disease
dc.subject.ucmGenética médica
dc.subject.ucmHematología
dc.subject.unesco2410.07 Genética Humana
dc.subject.unesco3205.04 Hematología
dc.titleA Novel Splicing Mutation in the ACVRL1/ALK1 Gene as a Cause of HHT2
dc.typejournal article
dc.volume.number11
dspace.entity.typePublication
relation.isAuthorOfPublication963e050e-5a67-40d7-8e25-3dc7ff5a8619
relation.isAuthorOfPublication.latestForDiscovery963e050e-5a67-40d7-8e25-3dc7ff5a8619
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