The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population.

Ataxia Autosomal recessive cerebellar ataxia Hereditary cerebellar ataxia Iranian population Spinocerebellar ataxia

Journal

Human genomics
ISSN: 1479-7364
Titre abrégé: Hum Genomics
Pays: England
ID NLM: 101202210

Informations de publication

Date de publication:
03 Apr 2024
Historique:
received: 14 01 2024
accepted: 14 03 2024
medline: 4 4 2024
pubmed: 4 4 2024
entrez: 3 4 2024
Statut: epublish

Résumé

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. 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). 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

DOI: 10.1186/s40246-024-00598-5 PMID: 38570878
pubmed: 38570878
doi: 10.1186/s40246-024-00598-5
pii: 10.1186/s40246-024-00598-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

35

Informations de copyright

© 2024. The Author(s).

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Auteurs

Nejat Mahdieh (N)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Institute, Iran University of Medical Sciences, Tehran, Iran.

Morteza Heidari (M)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Zahra Rezaei (Z)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Ali Reza Tavasoli (AR)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Pediatric Headache Program, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA.

Sareh Hosseinpour (S)

Department of Pediatrics, Division of Paediatric Neurology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

Maryam Rasulinejad (M)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Ali Zare Dehnavi (AZ)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Masoud Ghahvechi Akbari (M)

Physical Medicine and Rehabilitation Department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Reza Shervin Badv (RS)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Elahe Vafaei (E)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Ali Mohebbi (A)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Pouria Mohammadi (P)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Seyyed Mohammad Mahdi Hosseiny (SMM)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Reza Azizimalamiri (R)

Division of Pediatric Neurology, Department of Pediatrics, Golestan Medical, Educational and Research Center, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.

Ali Nikkhah (A)

Department of Pediatrics, Division of Paediatric Neurology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pediatrics, Division of Paediatric Neurology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Elham Pourbakhtyaran (E)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Mohammad Rohani (M)

Department of Neurology, School of Medicine, Hazrat Rasool-E Akram General Hospital, Iran University of Medical Sciences, Tehran, Iran.

Narges Khanbanha (N)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Sedigheh Nikbakht (S)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Mojtaba Movahedinia (M)

Children Growth Disorders Research Center, Department of Pediatric, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Parviz Karimi (P)

Department of Pediatric Diseases, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

Homa Ghabeli (H)

Department of Pediatrics, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Seyed Ahmad Hosseini (SA)

Department of Pediatrics, Taleghani Children's Hospital, Golestan University of Medical Sciences, Gorgan, Iran.

Fatemeh Sadat Rashidi (FS)

Neuroscience Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

Masoud Garshasbi (M)

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Morteza Rezvani Kashani (MR)

Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Noor M Ghiasvand (NM)

Department of Biology, Grand Valley State University, Allendale, MI, 49401, USA.

Stephan Zuchner (S)

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, USA.

Matthis Synofzik (M)

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.

Mahmoud Reza Ashrafi (MR)

Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. ashrafim@tums.ac.ir.
Department of Pediatrics, Division of Paediatric Neurology, Growth and Development Research Center, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. ashrafim@tums.ac.ir.

Classifications MeSH