Familial primary lateral sclerosis or dementia associated with Arg573Gly TBK1 mutation

Primary lateral sclerosis (PLS) is a rare variant of motor neuron disease (MND) characterised by selective upper motor neuron features whose causes and pathogenic mechanisms remain largely unknown. While some familial cases of childhood to young–adult onset with recessive transmission have been reported in association with mutations in the Alsin, SPG11 and SPG7 genes,1 most adult cases occur sporadically. Recently, Tank-binding kinase 1 (TBK1) mutations have been identified in 1.9% of frontotemporal dementia(FTD) and/or Amyotrophic lateral sclerosis (ALS) cohorts.2 However, pathogenicity of many TBK1 missense mutations is difficult to establish in the absence of cosegregation data. A screening for TBK1 mutations carried out by the European Early-Onset Dementia (EU EOD) Consortium in a large series of FTD/ALS cases found one carrier of the Arg573Gly mutation.3 The index case belonged to a Spanish family with autosomal dominant disease manifesting in the sixth decade as...

Source: Journal of Neurology, Neurosurgery and Psychiatry - October 9, 2017 Category: Neurosurgery Authors: Gomez-Tortosa, E., Van der Zee, J., Ruggiero, M., Gijselinck, I., Esteban-Perez, J., Garcia-Redondo, A., Borrego-Hernandez, D., Navarro, E., Sainz, M. J., Perez-Perez, J., Cruts, M., Van Broeckhoven, C., Guerrero-Lopez, R., on behalf of the EU EOD Consort Tags: PostScript Source Type: research