The molecular basis of human congenital limb malformations.
Wiley Interdiscip Rev Dev Biol
; 1(6): 803-22, 2012.
Article
em En
| MEDLINE
| ID: mdl-23799625
ABSTRACT
This review focuses predominantly on the human congenital malformations caused by alterations affecting the morphoregulatory gene networks that control early limb bud patterning and outgrowth. Limb defects are among the most frequent congenital malformations in humans that are caused by genetic mutations or teratogenic effects resulting either in abnormal, loss of, or additional skeletal elements. Spontaneous and engineered mouse models have been used to identify and study the molecular alterations and disrupted gene networks that underlie human congenital limb malformations. More recently, mouse genetics has begun to reveal the alterations that affect the often-large cis-regulatory landscapes that control gene expression in limb buds and cause devastating effects on limb bud development. These findings have paved the way to identifying mutations in cis-regulatory regions as causal to an increasing number of congenital limb malformations in humans. In these cases, no mutations in the coding region of a presumed candidate were previously detected. This review highlights how the current understanding of the molecular gene networks and interactions that control mouse limb bud development provides insight into the etiology of human congenital limb malformations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deformidades Congênitas dos Membros
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Wiley Interdiscip Rev Dev Biol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Suíça