BMS1 is mutated in aplasia cutis congenita.
Aplasia 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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-06-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3681727?pdf=render |
| _version_ | 1818056172872138752 |
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| author | Alexander G Marneros |
| author_facet | Alexander G Marneros |
| author_sort | Alexander G Marneros |
| collection | DOAJ |
| description | Aplasia 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. |
| first_indexed | 2024-12-10T12:24:37Z |
| format | Article |
| id | doaj.art-da93b822c0a34527b2388607e4e32048 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-10T12:24:37Z |
| publishDate | 2013-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-da93b822c0a34527b2388607e4e320482022-12-22T01:49:00ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-06-0196e100357310.1371/journal.pgen.1003573BMS1 is mutated in aplasia cutis congenita.Alexander G MarnerosAplasia 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.http://europepmc.org/articles/PMC3681727?pdf=render |
| spellingShingle | Alexander G Marneros BMS1 is mutated in aplasia cutis congenita. PLoS Genetics |
| title | BMS1 is mutated in aplasia cutis congenita. |
| title_full | BMS1 is mutated in aplasia cutis congenita. |
| title_fullStr | BMS1 is mutated in aplasia cutis congenita. |
| title_full_unstemmed | BMS1 is mutated in aplasia cutis congenita. |
| title_short | BMS1 is mutated in aplasia cutis congenita. |
| title_sort | bms1 is mutated in aplasia cutis congenita |
| url | http://europepmc.org/articles/PMC3681727?pdf=render |
| work_keys_str_mv | AT alexandergmarneros bms1ismutatedinaplasiacutiscongenita |