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.