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

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

Mahdieh N^{1, 2} ; Heidari M¹ ; Rezaei Z¹ ; Tavasoli AR^{1, 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

Mahdieh N^{1, 2}
Heidari M¹
Rezaei Z¹
Tavasoli AR^{1, 3}
Hosseinpour S⁴
Rasulinejad M¹
Dehnavi AZ¹
Ghahvechi Akbari M⁵
Badv RS¹
Vafaei E¹
Mohebbi A¹
Mohammadi P¹
Hosseiny SMM¹
Azizimalamiri R⁶
Nikkhah A^{4, 7}
Pourbakhtyaran E¹
Rohani M⁸
Khanbanha N¹
Nikbakht S¹
Movahedinia M⁹
Karimi P¹⁰
Ghabeli H¹¹
Hosseini SA¹²
Rashidi FS¹³
Garshasbi M¹⁴
Kashani MR¹⁵
Ghiasvand NM¹⁶
Zuchner S¹⁷
Synofzik M^{18, 19}
Ashrafi MR^{1, 20}

Show Affiliations

1. Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Childrenâ€™s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
2. Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Institute, Iran University of Medical Sciences, Tehran, Iran
3. Pediatric Headache Program, Barrow Neurological Institute, Phoenix Childrenâ€™s Hospital, Phoenix, AZ, United States
4. Department of Pediatrics, Division of Paediatric Neurology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
5. Physical Medicine and Rehabilitation Department, Childrenâ€™s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
6. Division of Pediatric Neurology, Department of Pediatrics, Golestan Medical, Educational and Research Center, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
7. Department of Pediatrics, Division of Paediatric Neurology, Mofid Childrenâ€™s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
8. Department of Neurology, School of Medicine, Hazrat Rasool-E Akram General Hospital, Iran University of Medical Sciences, Tehran, Iran
9. Children Growth Disorders Research Center, Department of Pediatric, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
10. Department of Pediatric Diseases, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
11. Department of Pediatrics, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
12. Department of Pediatrics, Taleghani Childrenâ€™s Hospital, Golestan University of Medical Sciences, Gorgan, Iran
13. Neuroscience Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
14. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
15. Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
16. Department of Biology, Grand Valley State University, Allendale, 49401, MI, United States
17. Department of Human Genetics and John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation, University of Miami Miller School of Medicine, Miami, FL, United States
18. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tubingen, Tubingen, Germany
19. Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany
20. Department of Pediatrics, Division of Paediatric Neurology, Growth and Development Research Center, Pediatrics Center of Excellence, Childrenâ€™s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

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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Mahmoudreza Ashrafi (4)

Behdad Gharib (1)

Style	Citing Format
MLA	Mahdieh N, et al.. "The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population." Human Genomics, vol. 18, no. 1, 2024, pp. -.
APA	Mahdieh N, Heidari M, Rezaei Z, Tavasoli AR, Hosseinpour S, Rasulinejad M, Dehnavi AZ, Ghahvechi Akbari M, Badv RS, Vafaei E, Mohebbi A, Mohammadi P, Hosseiny SMM, Azizimalamiri R, Nikkhah A, Pourbakhtyaran E, Rohani M, Khanbanha N, Nikbakht S, ... Ashrafi MR (2024). The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population. Human Genomics, 18(1), -.
Chicago	Mahdieh N, Heidari M, Rezaei Z, Tavasoli AR, Hosseinpour S, Rasulinejad M, Dehnavi AZ, et al.. "The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population." Human Genomics 18, no. 1 (2024): -.
Harvard	Mahdieh N et al. (2024) 'The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population', Human Genomics, 18(1), pp. -.
Vancouver	Mahdieh N, Heidari M, Rezaei Z, Tavasoli AR, Hosseinpour S, Rasulinejad M, et al.. The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population. Human Genomics. 2024;18(1):-.
BibTex	@article{ author = {Mahdieh N and Heidari M and Rezaei Z and Tavasoli AR and Hosseinpour S and Rasulinejad M and Dehnavi AZ and Ghahvechi Akbari M and Badv RS and Vafaei E and Mohebbi A and Mohammadi P and Hosseiny SMM and Azizimalamiri R and Nikkhah A and Pourbakhtyaran E and Rohani M and Khanbanha N and Nikbakht S and Movahedinia M and Karimi P and Ghabeli H and Hosseini SA and Rashidi FS and Garshasbi M and Kashani MR and Ghiasvand NM and Zuchner S and Synofzik M and Ashrafi MR}, title = {The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population}, journal = {Human Genomics}, volume = {18}, number = {1}, pages = {-}, year = {2024} }
RIS	TY - JOUR AU - Mahdieh N AU - Heidari M AU - Rezaei Z AU - Tavasoli AR AU - Hosseinpour S AU - Rasulinejad M AU - Dehnavi AZ AU - Ghahvechi Akbari M AU - Badv RS AU - Vafaei E AU - Mohebbi A AU - Mohammadi P AU - Hosseiny SMM AU - Azizimalamiri R AU - Nikkhah A AU - Pourbakhtyaran E AU - Rohani M AU - Khanbanha N AU - Nikbakht S AU - Movahedinia M AU - Karimi P AU - Ghabeli H AU - Hosseini SA AU - Rashidi FS AU - Garshasbi M AU - Kashani MR AU - Ghiasvand NM AU - Zuchner S AU - Synofzik M AU - Ashrafi MR TI - The Genetic Basis of Early-Onset Hereditary Ataxia in Iran: Results of a National Registry of a Heterogeneous Population JO - Human Genomics VL - 18 IS - 1 SP - EP - PY - 2024 ER -

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