Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/51517
Registo completo
Campo DC | Valor | Idioma |
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dc.contributor.author | Seabra, Catarina M. | por |
dc.contributor.author | Szoko, Nicholas | por |
dc.contributor.author | Erdin, Serkan | por |
dc.contributor.author | Ragavendran, Ashok | por |
dc.contributor.author | Stortchevoi, Alexei | por |
dc.contributor.author | Maciel, P. | por |
dc.contributor.author | Lundberg, Kathleen | por |
dc.contributor.author | Schlatzer, Daniela | por |
dc.contributor.author | Smith, Janice | por |
dc.contributor.author | Talkowski, Michael E. | por |
dc.contributor.author | et. al. | por |
dc.date.accessioned | 2018-03-05T12:17:02Z | - |
dc.date.available | 2018-03-05T12:17:02Z | - |
dc.date.issued | 2017-09-21 | - |
dc.identifier.citation | Seabra, C. M., Szoko, N., Erdin, S., Ragavendran, A., Stortchevoi, A., Maciel, P., ... & Gusella, J. F. (2017). A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings. American Journal of Medical Genetics Part A, 173(9), 2478-2484 | por |
dc.identifier.issn | 1552-4833 | - |
dc.identifier.uri | https://hdl.handle.net/1822/51517 | - |
dc.description.abstract | Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic, and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech/language disorder with full scale IQ scores 78-98 and scattered academic skill levels, expanding the phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the ARID1B copy number gain. Principal component analysis revealed marked differentiation of the subject's lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1014 were significantly up- or down-regulated compared to controls (q<0.01). Pathway analysis revealed highly significant enrichment for canonical pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and chromosomal replication, among others. Network analyses revealed down-regulation of: (1) intracellular components involved in organization of membranes, organelles, and vesicles; (2) aspects of cell cycle control, signal transduction, and nuclear protein export; (3) ubiquitination and proteosomal function; and (4) aspects of mRNA synthesis/splicing. Further studies are needed to determine the detailed molecular and cellular mechanisms by which constitutional haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental disabilities. | por |
dc.description.sponsorship | FCT Fellowship SFRH/BD/52049/2012 to CMS, NIH grant GM061354 to JFG, and MET, SFARI grant 308955 to JFG and R00MH095867 to MET and Autism Research Institute grant to MRN | por |
dc.language.iso | eng | por |
dc.publisher | Wiley | por |
dc.rights | openAccess | por |
dc.subject | ARID1B | por |
dc.subject | Chromatin | por |
dc.subject | Development | por |
dc.subject | Intellectual disability | por |
dc.subject | Proteome | por |
dc.subject | Proteomic | por |
dc.subject | Regulation | por |
dc.subject | SWI/SNF | por |
dc.subject | SWI/SNF-A | por |
dc.subject | SWI | por |
dc.subject | SNF | por |
dc.title | A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.38327/full | por |
oaire.citationStartPage | 2478 | por |
oaire.citationEndPage | 2484 | por |
oaire.citationIssue | 9 | por |
oaire.citationVolume | 173 | por |
dc.date.updated | 2018-01-26T09:27:26Z | - |
dc.identifier.doi | 10.1002/ajmg.a.38327 | por |
dc.identifier.pmid | 28691782 | por |
dc.subject.fos | Ciências Médicas::Medicina Básica | por |
dc.description.publicationversion | info:eu-repo/semantics/publishedVersion | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | American Journal of Medical Genetics Part A | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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seabra_cm_2017_arid1b_dup.pdf | 706 kB | Adobe PDF | Ver/Abrir |