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Genetic Testing of Leukodystrophies Unraveling Extensive Heterogeneity in a Large Cohort and Report of Five Common Diseases and 38 Novel Variants Publisher Pubmed



Mahdieh N1, 2 ; Soveizi M2 ; Tavasoli AR3 ; Rabbani A1 ; Ashrafi MR3 ; Kohlschutter A4 ; Rabbani B1, 5
Authors
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Authors Affiliations
  1. 1. Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Myelin Disorders Clinic, Pediatric Neurology Division, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany
  5. 5. Iranian Comprehensive Hemophilia Care Center, Tehran, Iran

Source: Scientific Reports Published:2021


Abstract

This study evaluates the genetic spectrum of leukodystrophies and leukoencephalopathies in Iran. 152 children, aged from 1 day to 15 years, were genetically tested for leukodystrophies and leukoencephalopathies based on clinical and neuroradiological findings from 2016 to 2019. Patients with a suggestive specific leukodystrophy, e. g. metachromatic leukodystrophy, Canavan disease, Tay-Sachs disease were tested for mutations in single genes (108; 71%) while patients with less suggestive findings were evaluated by NGS. 108 of 152(71%) had MRI patterns and clinical findings suggestive of a known leukodystrophy. In total, 114(75%) affected individuals had (likely) pathogenic variants which included 38 novel variants. 35 different types of leukodystrophies and genetic leukoencephalopathies were identified. The more common identified disorders included metachromatic leukodystrophy (19 of 152; 13%), Canavan disease (12; 8%), Tay-Sachs disease (11; 7%), megalencephalic leukodystrophy with subcortical cysts (7; 5%), X-linked adrenoleukodystrophy (8; 5%), Pelizaeus–Merzbacher-like disease type 1 (8; 5%), Sandhoff disease (6; 4%), Krabbe disease (5; 3%), and vanishing white matter disease (4; 3%). Whole exome sequencing (WES) revealed 90% leukodystrophies and genetic leukoencephalopathies. The total diagnosis rate was 75%. This unique study presents a national genetic data of leukodystrophies; it may provide clues to the genetic pool of neighboring countries. Patients with clinical and neuroradiological evidence of a genetic leukoencephalopathy should undergo a genetic analysis to reach a definitive diagnosis. This will allow a diagnosis at earlier stages of the disease, reduce the burden of uncertainty and costs, and will provide the basis for genetic counseling and family planning. © 2021, The Author(s).
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