Mutations in GLE1, RNA export mediator (GLE1) gene have previously been shown to cause motor neuron diseases such as lethal congenital contracture syndrome 1 (LCCS1) and lethal arthrogryposis with anterior horn cell disease (LAAHD), including arthrogryposis, fetal akinesis and motor neuron loss as common clinical features.
We also suggest that lethal congenital contracture syndrome 1 (LCCS1) and lethal arthrogryposis with anterior horn disease (LAAHD), the two AMC subtypes related to GLE1, do not have sufficient clinical or molecular differentiation to be considered allelic disorders.
These results identify a mechanistic step in Gle1's mRNA export function at nuclear pore complexes and directly implicate altered export in LCCS1 disease pathology.
We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.