Weaver, K. Nicole and Watt, Kristin E. Noack and Hufnagel, Robert B. and Acedo, Joaquin Navajas and Linscott, Luke L. and Sund, Kristen L. and Bender, Patricia L. and Koenig, Rainer and Lourenco, Charles M. and Hehr, Ute and Hopkin, Robert J. and Lohmann, Dietmar R. and Trainor, Paul A. and Wieczorek, Dagmar and Saal, Howard M. (2015) Acrofacial Dysostosis, Cincinnati Type, a Mandibulofacial Dysostosis Syndrome with Limb Anomalies, Is Caused by POLR1A Dysfunction. AMERICAN JOURNAL OF HUMAN GENETICS, 96 (5). pp. 765-774. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
We report three individuals with a cranioskeletal malformation syndrome that we define as acrofacial dysostosis, Cincinnati type. Each individual has a heterozygous mutation in POLR1A, which encodes a core component of RNA polymerase 1. All three individuals exhibit varying degrees of mandibulofacial dysostosis, and two additionally have limb anomalies. Consistent with this observation, we discovered that polr1a mutant zebrafish exhibited cranioskeletal anomalies mimicking the human phenotype. polr1a loss of function led to perturbed ribosome biogenesis and p53-dependent cell death, resulting in a deficiency of neural-crest-derived skeletal precursor cells and consequently craniofacial anomalies. Our findings expand the genotypic and phenotypic heterogeneity of congenital acrofacial disorders caused by disruption of ribosome biogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RNA-POLYMERASE I; RIBOSOMAL-RNA; GENE-TRANSCRIPTION; P53; COLLINSSYNDROME,TREACHER; PATHOGENESIS; INHIBITION; BIOGENESIS; GENERATION; MUTATIONS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jul 2019 08:54 |
| Last Modified: | 18 Jul 2019 08:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5510 |
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