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

Autor: 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., Heidari M; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Rezaei Z; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., 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., Hosseinpour S; Department of Pediatrics, Division of Paediatric Neurology, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Rasulinejad M; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Dehnavi AZ; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Ghahvechi Akbari M; Physical Medicine and Rehabilitation Department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Badv RS; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Vafaei E; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Mohebbi A; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Mohammadi P; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Hosseiny SMM; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Azizimalamiri R; Division of Pediatric Neurology, Department of Pediatrics, Golestan Medical, Educational and Research Center, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran., 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., Pourbakhtyaran E; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Rohani M; Department of Neurology, School of Medicine, Hazrat Rasool-E Akram General Hospital, Iran University of Medical Sciences, Tehran, Iran., Khanbanha N; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Nikbakht S; Pediatric Neurology Division, Pediatrics Center of Excellence, Ataxia Clinic, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran., Movahedinia M; Children Growth Disorders Research Center, Department of Pediatric, Shahid Sadoughi University of Medical Sciences, Yazd, Iran., Karimi P; Department of Pediatric Diseases, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran., Ghabeli H; Department of Pediatrics, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran., Hosseini SA; Department of Pediatrics, Taleghani Children's Hospital, Golestan University of Medical Sciences, Gorgan, Iran., Rashidi FS; Neuroscience Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran., Garshasbi M; Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Kashani MR; Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran., Ghiasvand NM; Department of Biology, Grand Valley State University, Allendale, MI, 49401, USA., 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., 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., 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.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2024 Apr 03; Vol. 18 (1), pp. 35. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1186/s40246-024-00598-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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