Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly.
Mol Genet Metab
; 98(1-2): 225-34, 2009.
Article
en En
| MEDLINE
| ID: mdl-19553149
ABSTRACT
The cyclopic and laterality phenotypes in model organisms linked to disturbances in the generation or propagation of Nodal-like signals are potential examples of similar impairments resulting in birth defects in humans. However, the types of gene mutation(s) and their pathogenetic combinations in humans are poorly understood. Here we describe a mutational analysis of the human NODAL gene in a large panel of patients with phenotypes compatible with diminished NODAL ligand function. Significant reductions in the biological activity of NODAL alleles are detected among patients with congenital heart defects (CHD), laterality anomalies (e.g. left-right mis-specification phenotypes), and only rarely holoprosencephaly (HPE). While many of these NODAL variants are typical for family-specific mutations, we also report the presence of alleles with significantly reduced activity among common population variants. We propose that some of these common variants act as modifiers and contribute to the ultimate phenotypic outcome in these patients; furthermore, we draw parallels with strain-specific modifiers in model organisms to bolster this interpretation.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Holoprosencefalia
/
Proteína Nodal
/
Cardiopatías Congénitas
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Genet Metab
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos