Acrofacial Dysostosis, Cincinnati Type, a Mandibulofacial Dysostosis Syndrome with Limb Anomalies, Is Caused by POLR1A Dysfunction.
Am J Hum Genet
; 96(5): 765-74, 2015 May 07.
Article
en En
| MEDLINE
| ID: mdl-25913037
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ribosomas
/
ARN Polimerasa I
/
Deformidades Congénitas de las Extremidades
/
Disostosis Mandibulofacial
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Hum Genet
Año:
2015
Tipo del documento:
Article