Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly.

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 mutat

SUBMITTER: Roessler E 

PROVIDER: S-EPMC2774839 | biostudies-literature | 2009 Sep-Oct

REPOSITORIES: biostudies-literature