Large Proportion of Amyotrophic Lateral Sclerosis Cases in Sardinia Due to a Single Founder Mutation of the TARDBP Gene

Abstract

The identification of the transactivation response DNA-binding protein (TDP-43) as the major constituent of ubiquitin inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) was a major advance in our understanding of the pathogenesis of these neurodegenerative diseases.¹ Subsequently, it was discovered that mutations in the TARDBP gene located on chromosome 1p36 (which encodes the TDP-43 protein) explain approximately 4% of familial ALS cases² and a smaller proportion of FTD cases.³