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The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population Publisher Pubmed



Mahdieh N1, 2 ; Heidari M1 ; Rezaei Z1 ; Tavasoli AR1, 3 ; Hosseinpour S4 ; Rasulinejad M1 ; Dehnavi AZ1 ; Ghahvechi Akbari M5 ; Badv RS1 ; Vafaei E1 ; Mohebbi A1 ; Mohammadi P1 ; Hosseiny SMM1 ; Azizimalamiri R6 Show All Authors
Authors
  1. Mahdieh N1, 2
  2. Heidari M1
  3. Rezaei Z1
  4. Tavasoli AR1, 3
  5. Hosseinpour S4
  6. Rasulinejad M1
  7. Dehnavi AZ1
  8. Ghahvechi Akbari M5
  9. Badv RS1
  10. Vafaei E1
  11. Mohebbi A1
  12. Mohammadi P1
  13. Hosseiny SMM1
  14. Azizimalamiri R6
  15. Nikkhah A4, 7
  16. Pourbakhtyaran E1
  17. Rohani M8
  18. Khanbanha N1
  19. Nikbakht S1
  20. Movahedinia M9
  21. Karimi P10
  22. Ghabeli H11
  23. Hosseini SA12
  24. Rashidi FS13
  25. Garshasbi M14
  26. Kashani MR15
  27. Ghiasvand NM16
  28. Zuchner S17
  29. Synofzik M18, 19
  30. Ashrafi MR1, 20

Source: Human Genomics Published:2024


Abstract

Background: To investigate the genetics of early-onset progressive cerebellar ataxia in Iran, we conducted a study at the Children’s Medical Center (CMC), the primary referral center for pediatric disorders in the country, over a three-year period from 2019 to 2022. In this report, we provide the initial findings from the national registry. Methods: We selected all early-onset patients with an autosomal recessive mode of inheritance to assess their phenotype, paraclinical tests, and genotypes. The clinical data encompassed clinical features, the Scale for the Assessment and Rating of Ataxia (SARA) scores, Magnetic Resonance Imaging (MRI) results, Electrodiagnostic exams (EDX), and biomarker features. Our genetic investigations included single-gene testing, Whole Exome Sequencing (WES), and Whole Genome Sequencing (WGS). Results: Our study enrolled 162 patients from various geographic regions of our country. Among our subpopulations, we identified known and novel pathogenic variants in 42 genes in 97 families. The overall genetic diagnostic rate was 59.9%. Notably, we observed PLA2G6, ATM, SACS, and SCA variants in 19, 14, 12, and 10 families, respectively. Remarkably, more than 59% of the cases were attributed to pathogenic variants in these genes. Conclusions: Iran, being at the crossroad of the Middle East, exhibits a highly diverse genetic etiology for autosomal recessive hereditary ataxia. In light of this heterogeneity, the development of preventive strategies and targeted molecular therapeutics becomes crucial. A national guideline for the diagnosis and management of patients with these conditions could significantly aid in advancing healthcare approaches and improving patient outcomes. © The Author(s) 2024.
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