SHORT REPORTS ARSACS as a Worldwide Disease: Novel SACS Mutations Identified in a Consanguineous Family from the Remote Tribal Jammu and Kashmir Region in India Raja A. H. Kuchay 1 & Yaser Rafiq Mir 1 & Xue Zeng 2 & Asima Hassan 3 & Javed Musarrat 4 & Iqbal Parwez 4 & Christoph Kernstock 5 & Andreas Traschütz 6,7 & Matthis Synofzik 6,7 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract 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. Keywords ARSACS . Consanguinity . Whole exome . Tribal India . J&K Introduction Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) (Online Mendelian Inheritance in Man database [OMIM] #270550), caused by mutations in SACS, was first described 40 years ago in the regions of Charlevoix and Saguenay-Lac-St-Jean in Quebec, Canada [1]. It is classically characterized by a triad of slowly progressive early-onset cer- ebellar ataxia, pyramidal spasticity, and axonal-demyelinating sensorimotor peripheral neuropathy, later often complicated by frequent dysphagia [2, 3]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-019-01028-2) contains supplementary material, which is available to authorized users. * Raja A. H. Kuchay kuchay_bgsbu@yahoo.com 1 Department of Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, J&K 185234, India 2 Department of Genetics, Yale School of Medicine, New Haven, CT, USA 3 Department of Ophthalmology, Government Medical College, Srinagar, J&K, India 4 School of Biosciences & Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, J&K, India 5 University Eye Hospital Tübingen, University of Tübingen, Tübingen, Germany 6 Department of Neurodegenerative Diseases, Center for Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany 7 German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany The Cerebellum https://doi.org/10.1007/s12311-019-01028-2