ARSACS as a Worldwide Disease: Novel SACS Mutations Identified in a Consanguineous Family from the Remote Tribal Jammu and Kashmir Region in India
Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by the triad of early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lower limb spasticity. Here, we present a 28-year-old male patient with symptoms of ARSACS and mild intellectual disability from a consanguineous family of tribal J&K, India. Whole exome sequencing unraveled a novel homozygous frameshift SACS mutation (Cys2869ValfsTer15) in the patient. In addition to the well-established ARSACS imaging features, MRI revealed T2 hyperintense rim around the thalami (“bithalamic stripes”) demonstrating that this feature might serve as an additional supportive diagnostic imaging marker for ARSACS. Moreover, retinal nerve fiber layer thickening which has recently been proposed as a diagnostic biomarker for ARSACS was present on routine optic coherence tomography (OCT) also in this patient, indicating that it might indeed present a relatively universal diagnostic biomarker for ARSACS. In sum, our findings extend the geographical distribution of ARSACS to even very remote tribal regions in Asia (such as the Rajouri region of J&K, India) and extend the mutational and imaging spectrum of ARSACS. They provide further support that brain imaging and OCT markers might serve as diagnostic biomarkers for ARSACS in patients with novel SACS mutations, applicable even in remote regions of the world to identify and confirm ARSACS disease.
KeywordsARSACS Consanguinity Whole exome Tribal India J&K
We thank UGC, New Delhi, India for awarding Start Up grant to Dr. Raja Amir. We thank the patient and family for participation in this study. We thank Dr. A.A Shah, Associate Professor, School of Biosciences and Biotechnology for his motivation and regular inputs. We thank Dr. Susheel Verma, Dr. Tanvir-ul-Hassn, and Dr. Saima Aslam for their timely inputs.
Laboratory of Dr. Raja Amir was supported by UGC Start Up grant, New Delhi, India. This project was supported, in part, via the European Union’s Horizon 2020 research and innovation program under the ERA-NET Cofund action No. 643578. It was supported by the BMBF under the frame of the E-Rare-3 network PREPARE (01GM1607 to M. S).
Compliance with Ethical Standards
All the procedures described in the text have been conducted in accordance with ethical principles.
Conflict of Interest
The authors declare that they have no conflict of interests.
- 1.Bouchard JP, Barbeau A, Bouchard R, Bouchard RW. Autosomal recessive spastic ataxia of Charlevoix Saguenay. Can J Neurol Sci. 1978;5:61–9.Google Scholar
- 4.Ogawa T, Takiyama Y, Sakoe K, Mori K, Namekawa M, Shimazaki H, et al. Identification of a SACS gene missense mutation in ARSACS. Neurology. 2004;62:107–9. https://doi.org/10.1212/01.WNL.0000099371.14478.73.CrossRefGoogle Scholar