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dc.creatorMondéjar, Rufinoes
dc.creatorSolano Manchego, Franciscaes
dc.creatorRubio, Rocíoes
dc.creatorDelgado, Mercedeses
dc.creatorPérez Sempere, Ángeles
dc.creatorGonzález Meneses, Antonioes
dc.creatorVendrell, Teresaes
dc.creatorIzquierdo Ayuso, Guillermoes
dc.creatorMartínez Mir, Amaliaes
dc.creatorLucas Lucas, Migueles
dc.date.accessioned2022-01-31T10:22:44Z
dc.date.available2022-01-31T10:22:44Z
dc.date.issued2014
dc.identifier.issn1932-6203es
dc.identifier.urihttps://hdl.handle.net/11441/129439
dc.description.abstractObjective: To study the molecular genetic and clinical features of cerebral cavernous malformations (CCM) in a cohort of Spanish patients. Methods: We analyzed the CCM1, CCM2, and CCM3 genes by MLPA and direct sequencing of exons and intronic boundaries in 94 familial forms and 41 sporadic cases of CCM patients of Spanish extraction. When available, RNA studies were performed seeking for alternative or cryptic splicing. Results: A total of 26 pathogenic mutations, 22 of which predict truncated proteins, were identified in 29 familial forms and in three sporadic cases. The repertoire includes six novel non-sense and frameshift mutations in CCM1 and CCM3. We also found four missense mutations, one of them located at the third NPXY motif of CCM1 and another one that leads to cryptic splicing of CCM1 exon 6. We found four genomic deletions with the loss of the whole CCM2 gene in one patient and a partial loss of CCM1and CCM2 genes in three other patients. Four families had mutations in CCM3. The results include a high frequency of intronic variants, although most of them localize out of consensus splicing sequences. The main symptoms associated to clinical debut consisted of cerebral haemorrhage, migraines and epileptic seizures. The rare co-occurrence of CCM with Noonan and Chiari syndromes and delayed menarche is reported. Conclusions: Analysis of CCM genes by sequencing and MLPA has detected mutations in almost 35% of a Spanish cohort (36% of familial cases and 10% of sporadic patients). The results include 13 new mutations of CCM genes and the main clinical symptoms that deserves consideration in molecular diagnosis and genetic counselling of cerebral cavernous malformations.es
dc.description.sponsorshipInstituto de Salud Carlos III CP10/00526es
dc.description.sponsorshipJunta de Andalucía P07-CVI-02790es
dc.description.sponsorshipFundación José Luis Castañoes
dc.formatapplication/pdfes
dc.format.extent8es
dc.language.isoenges
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAdolescentes
dc.subjectAdultes
dc.subjectAged, 80 and overes
dc.subjectApoptosis Regulatory Proteins / geneticses
dc.subjectBase Sequencees
dc.subjectCarrier Proteins / geneticses
dc.subjectChildes
dc.subjectCodon, Nonsensees
dc.subjectDNA Mutational Analysises
dc.subjectGene Frequencyes
dc.subjectHemangioma, Cavernous, Central Nervous Systemes
dc.subjectKRIT1 Proteines
dc.subjectMembrane Proteins / geneticses
dc.subjectMicrotubule-Associated Proteins / geneticses
dc.subjectPolymorphism, Single Nucleotidees
dc.subjectPrevalencees
dc.subjectProto-Oncogene Proteins / geneticses
dc.subjectSequence Deletiones
dc.subjectYoung Adultes
dc.titleMutation Prevalence of Cerebral Cavernous Malformation Genes in Spanish Patientses
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.identifier.doi10.1371/journal.pone.0086286es
dc.contributor.groupUniversidad de Sevilla. CTS399: Neuromedicina Moleculares
dc.journaltitlePLOS ONEes
dc.publication.volumen9es
dc.publication.issue1es
dc.publication.initialPage1es
dc.publication.endPage8es

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