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. KuchayEmail author
  • Yaser Rafiq Mir
  • Xue Zeng
  • Asima Hassan
  • Javed Musarrat
  • Iqbal Parwez
  • Christoph Kernstock
  • Andreas Traschütz
  • Matthis Synofzik
Short Reports


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.


ARSACS 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.

Funding Information

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.

Supplementary material

12311_2019_1028_MOESM1_ESM.docx (247 kb)
ESM 1 (DOCX 247 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Raja A. H. Kuchay
    • 1
    Email author
  • 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
  1. 1.Department of BiotechnologyBaba Ghulam Shah Badshah UniversityRajouriIndia
  2. 2.Department of GeneticsYale School of MedicineNew HavenUSA
  3. 3.Department of OphthalmologyGovernment Medical CollegeSrinagarIndia
  4. 4.School of Biosciences & BiotechnologyBaba Ghulam Shah Badshah UniversityRajouriIndia
  5. 5.University Eye Hospital TübingenUniversity of TübingenTübingenGermany
  6. 6.Department of Neurodegenerative Diseases, Center for Neurology and Hertie-Institute for Clinical Brain ResearchUniversity of TübingenTübingenGermany
  7. 7.German Center for Neurodegenerative Diseases (DZNE)TübingenGermany

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