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. ©2012 American Medical Association. All rights reserved.