Transmission and Phenotype Genotype Correlation

Two thirds of the JAG1 mutations are de novo. No phenotypic difference is observed between patients with or without visible rearrangement in 20p12, neither between patients with and without an identified mutation in

JAG1 gene encodes a transmembrane protein belonging to the family of Notch ligands. Notch signaling pathway seems to control the ability of a broad spectrum of precursor cells to progress to a more differentiated state both during development and oncogenesis.1-16'17-1 Analysis of JAG1 expression during human development demonstrates that renal manifestations and other miscellaneous features previously described were not coincidental.1-18-1

The mechanism causing AGS may involve haploin-sufficiency or a dominant negative effect. Most of the mutations (70%) introduce premature stop codon, which is expected to result in truncated secreted proteins. Such truncated Notch ligands in Drosophila have a dominant negative effect.[19] However, corresponding mRNA may be degraded by nonsense mediated RNA decay, resulting in a haploinsufficiency state comparable to the entire deletion of the gene.[20]

JAG1 mutations are identified in 70% of AGS patients; although alteration outside the coding sequence is still possible, the involvement of other components of Notch signaling pathway either as another disease-causing gene or as a modifier is very likely. This hypothesis is supported by recent demonstration that hypomorphic allele of Notch2 may be both responsible for bile duct paucity and acts as a genetic modifier of Jag1 haploin-sufficiency in a mice model.[21]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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