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

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay in the Time of Next-Generation Sequencing—Reply

“…1 As pointed out in our original article, we appreciate that some of the features we observed within the brother and sister fell within the previously described clinical spectrum associated with mutations in this gene. 1,2 However, onset in adult life is unusual, and a prominent sensorimotor neuropathy resembling Charcot-Marie-Tooth disease is not usually found. 3 Thus, SACS is not the first disease gene that comes to mind for the family we described.…”

“…3 Thus, SACS is not the first disease gene that comes to mind for the family we described. 1 In recent years, there has been an almost exponential increase in the number of different disease genes shown to cause autosomal recessive spastic ataxia. 4 Although some can be distinguished on clinical grounds, in many patients, it is not possible to do this with confidence.…”

Abnormal retinal thickening is a common feature among patients with ARSACS-related phenotypes: Table 1

“…The molecular genetic characterisation of these four patients with next-generation whole exome sequencing has been previously reported 4 5. All the patients presented with progressive gait ataxia and they were severely disabled, requiring the use of a wheelchair for ambulation.…”

“…4 5 Topographic analysis of the optic disc was performed with the Spectralis optical coherence tomography (OCT) platform (Heidelberg Engineering, Heidelberg, Germany).…”

Exome sequencing: how to understand it

“…For example, exome sequencing in patients with an unexplained peripheral neuropathy and phenotype similar to Charcot–Marie–Tooth disease found novel mutations in the SACS gene, previously known to cause autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) 13. Sanger sequencing of the SACS gene was not originally performed because ARSACS is associated with a childhood onset spastic ataxia, and not Charcot–Marie–Tooth disease.…”