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.