De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome.
Nat Genet
; 44(4): 440-4, S1-2, 2012 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-22366783
ABSTRACT
Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
/
Encéfalo
/
Actinas
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Genet
Ano de publicação:
2012
Tipo de documento:
Article