Two German Kindreds With Familial Amyotrophic Lateral Sclerosis Due to TARDBP Mutations

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder leading to degeneration of upper and lower motor neurons in the brain and spinal cord. Clinical hallmarks are spasticity, brisk tendon reflexes, pyramidal signs, and progressive atrophy and weakness of the skeletal musculature. The patients die within a few years after onset, usually of respiratory failure.¹ Most cases are sporadic (sALS), but about 10% are familial (fALS). About 15% to 20% of patients with autosomal dominant fALS have mutations in the superoxide dismutase gene (SOD1),² while mutations in other genes (including senataxin [OMIM 608465],³ dynactin 1 [OMIM 601143],⁴ and vesicle-associated membrane protein B [OMIM 605704]⁵) are described as rare causes of fALS.