کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1998936 1541567 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 98, Issues 1–2, October 2009, Pages 225–234
نویسندگان
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