A rare genetic variant in APEX1 is associated with fALS. APEX1 in fALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons and progressive muscle weakness. We aimed to locate the pathogenic mutations in familial ALS (fALS) pedigrees and to understand how they affect the disease phenotype. We analyzed whole-genome sequencing data of fALS probands without the most common disease-causing mutations, and identified a rare missense variant in APEX1 associated with ALS in one pedigree. Patients carrying the mutation are characterized by early onset, lower motor neuron onset, and long survival. This study provided evidence linking APEX1 polymorphism with fALS and information on the distinct clinical manifestation.