Prominent Sensorimotor Neuropathy Due to SACS Mutations Revealed by Whole-Exome Sequencing

OBJECTIVE: To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings. DESIGN: Case reports and whole-exome DNA sequencing. SETTING: Neurogenetics clinic, Institute of Genetic Medicine, Newcastle upon Tyne, England. PATIENTS: Two adult siblings with a sensorimotor neuropathy, ataxia, and spasticity. MAIN OUTCOME MEASURES: Clinical, neurophysiological, imaging, and genetic data. RESULTS: Novel compound heterozygous frameshift mutations were detected in the SACS gene of both siblings, predicted to drastically truncate the sacsin protein. CONCLUSIONS: Whole-exome sequencing rapidly defined the genetic cause of the disorder, expanding the clinical phenotype associated with SACS mutations to include a severe sensorimotor neuropathy.