POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism.
Am J Hum Genet
; 91(2): 330-6, 2012 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-22840364
ABSTRACT
Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Centríolos
/
Cílios
/
Nanismo
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Arábia Saudita