Anti-Progranulin monoclonal antibody, clone 444830 [Biotin]

We describe a sporadic amyotrophic lateral sclerosis (ALS) patient who presented rapid progress of muscle weakness and died of respiratory failure one and a half years after onset. Genetic analysis revealed a novel ALS-causing gene NEK1 nonsense mutation p.K1210* and a known pathogenic frontotemporal lobar degeneration (FTD)-causing gene GRN mutation p.C139R. It is rare for ALS patients to carry two different pathogenic mutations simultaneously. The individual only had typically motor neuron dysfunction without any related cognitive symptoms. GRN p.C139R mutation is linked to various clinical phenotypes that include FTD and Alzheimer's disease (AD). The case carrying two different gene mutations expands our understanding of ALS genetics.

The enteric nervous system (ENS) predominantly originates from vagal neural crest (VNC) cells that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies.