Inclusion body myopathy (IBM) associated with Paget disease of the bone, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), sometimes called IBMPFD/ALS or multi system proteinopathy, is a rare, autosomal dominant disorder characterized by progressive degeneration of muscle, brain, motor neurons, and bone with prominent TDP-43 pathology. Recently, 2 novel genes for multi system proteinopathy were discovered; heterogenous nuclear ribonucleoprotein (hnRNP) A1 and A2B1. Subsequently, a mutation in hnRNPA1 was also identified in a pedigree with autosomal dominant familial ALS. The genetic evidence for ALS and other neurodegenerative diseases is still insufficient. We therefore sequenced the prion-like domain of these genes in 135 familial ALS, 1084 sporadic ALS, 68 familial FTD, 74 sporadic FTD, and 31 sporadic IBM patients in a Dutch population. We did not identify any mutations in these genes in our cohorts. Mutations in hnRNPA1 and hnRNPA2B1 prove to be a rare cause of ALS, FTD, and IBM in the Netherlands.

Amyotrophic lateral sclerosis (ALS), Frontotemporal dementia (FTD), HnRNPA1, HnRNPA2B1, Inclusion body myopathy (IBM)
dx.doi.org/10.1016/j.neurobiolaging.2014.01.152, hdl.handle.net/1765/61781
Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology
This work was funded by the European Commission 7th Framework Programme; grant id fp7/259867 - European multidisciplinary ALS network identification to cure motor neuron degeneration (EURO-MOTOR)
Department of Neurology

Seelen, M, Visser, A.E, Overste, D.J, Kim, H.J, Palud, A, Wong, T.H, … van den Berg, L.H. (2014). No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology, 35(8). doi:10.1016/j.neurobiolaging.2014.01.152