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dc.contributor.authorMarneros, Alexander G.en_US
dc.date.accessioned2014-02-13T19:01:44Z
dc.date.issued2013en_US
dc.identifier.citationMarneros, Alexander G. 2013. “BMS1 Is Mutated in Aplasia Cutis Congenita.” PLoS Genetics 9 (6): e1003573. doi:10.1371/journal.pgen.1003573. http://dx.doi.org/10.1371/journal.pgen.1003573.en
dc.identifier.issn1553-7390en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11708612
dc.description.abstractAplasia cutis congenita (ACC) manifests with localized skin defects at birth of unknown cause, mostly affecting the scalp vertex. Here, genome-wide linkage analysis and exome sequencing was used to identify the causative mutation in autosomal dominant ACC. A heterozygous Arg-to-His missense mutation (p.R930H) in the ribosomal GTPase BMS1 is identified in ACC that is associated with a delay in 18S rRNA maturation, consistent with a role of BMS1 in processing of pre-rRNAs of the small ribosomal subunit. Mutations that affect ribosomal function can result in a cell cycle defect and ACC skin fibroblasts with the BMS1 p.R930H mutation show a reduced cell proliferation rate due to a p21-mediated G1/S phase transition delay. Unbiased comparative global transcript and proteomic analyses of ACC fibroblasts with this mutation confirm a central role of increased p21 levels for the ACC phenotype, which are associated with downregulation of heterogenous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich splicing factors (SRSFs). Functional enrichment analysis of the proteomic data confirmed a defect in RNA post-transcriptional modification as the top-ranked cellular process altered in ACC fibroblasts. The data provide a novel link between BMS1, the cell cycle, and skin morphogenesis.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pgen.1003573en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681727/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectGeneticsen
dc.subjectGenetics of Diseaseen
dc.subjectHuman Geneticsen
dc.subjectMedicineen
dc.subjectDermatologyen
dc.titleBMS1 Is Mutated in Aplasia Cutis Congenitaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Geneticsen
dash.depositing.authorMarneros, Alexander G.en_US
dc.date.available2014-02-13T19:01:44Z
dc.identifier.doi10.1371/journal.pgen.1003573*
dash.contributor.affiliatedMarneros, Alexander


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