Exome sequencing: an efficient diagnostic tool for complex neurodegenerative disorders

Background and purpose Autosomal recessive cerebellar ataxia (ARCA) comprises a large and heterogeneous group of neurodegenerative disorders. We studied three families diagnosed with ARCA. Methods To determine the gene lesions responsible for their disorders, we performed high‐density single‐nucleotide polymorphism genotyping and exome sequencing. Results We identified a new mutation in the SACS gene and a known mutation in SPG11. Notably, we also identified a homozygous variant in APOB, a gene previously associated with ataxia. Conclusions These findings demonstrate that exome sequencing is an efficient and direct diagnostic tool for identifying the causes of complex and genetically heterogeneous neurodegenerative diseases, early‐stage disease or cases with limited clinical data.