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Clinical and Molecular Findings of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay: An Iranian Case Series Expanding the Genetic and Neuroimaging Spectra Publisher Pubmed



Ashrafi MR1, 2 ; Mohammadi P1, 3 ; Tavasoli AR1, 4, 5 ; Heidari M1, 4 ; Hosseinpour S1, 6 ; Rasulinejad M1 ; Rohani M7 ; Akbari MG1, 8 ; Malamiri RA9 ; Badv RS1 ; Fathi D10, 11 ; Dehnavi AZ1 ; Savad S12 ; Rabbani A1, 2 Show All Authors
Authors
  1. Ashrafi MR1, 2
  2. Mohammadi P1, 3
  3. Tavasoli AR1, 4, 5
  4. Heidari M1, 4
  5. Hosseinpour S1, 6
  6. Rasulinejad M1
  7. Rohani M7
  8. Akbari MG1, 8
  9. Malamiri RA9
  10. Badv RS1
  11. Fathi D10, 11
  12. Dehnavi AZ1
  13. Savad S12
  14. Rabbani A1, 2
  15. Synofzik M13, 14
  16. Mahdieh N15
  17. Rezaei Z1
Show Affiliations
Authors Affiliations
  1. 1. Pediatric Neurology Division, Children’s Medical Center, Pediatrics Center of Excellence, Ataxia Clinic, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pediatrics Center, Growth and Development Research Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Faculty of Medical Sciences, Department of Medical Genetics, Tarbiat Modares University, Tehran, Iran
  4. 4. Pediatric Neurology Division, Children’s Medical Center, Pediatrics Center of Excellence, Myelin Disorders Clinic, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, United States
  6. 6. Department of Pediatric Neurology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Neurology, School of Medicine, Hazrat Rasool-E Akram General Hospital, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Physical Medicine and Rehabilitation Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Division of Pediatric Neurology, Department of Pediatrics, Golestan Medical, Educational and Research Center, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
  10. 10. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
  13. 13. Division Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tubingen, Tubingen, Germany
  14. 14. Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany
  15. 15. Cardiogenetic Research Center, Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Source: Cerebellum Published:2023


Abstract

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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