Affiliation:
1. Department of Neurology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China
2. NHC Key Laboratory of Prevention and treatment of Cerebrovascular Disease Zhengzhou Henan China
3. Institute of Neuroscience Zhengzhou University Zhengzhou Henan China
4. Henan Key Laboratory of Cerebrovascular Diseases Zhengzhou University Zhengzhou Henan China
Abstract
AbstractObjectiveLeukoencephalopathies are a group of heterogeneous disorders characterized by the degeneration of white matter, resulting in a variety of progressive neurological symptoms. To date, over 60 genes linked to genetic leukoencephalopathies have been discovered through whole‐exome sequencing (WES) and long‐read sequencing. Nonetheless, the genetic diversity and clinical variability of these disorders among various racial groups remain largely unknown. Therefore, this study aims to analyze the genetic spectrum and clinical features of Chinese adult leukoencephalopathies and compare the genetic profiles in different populations.MethodsA total of 129 patients suspected of possible genetic leukoencephalopathy were enrolled and underwent WES and dynamic mutation analysis. Bioinformatics tools were used to predict the pathogenicity of these mutations. Skin biopsies were conducted for further diagnosis. Genetic data sources from different populations were collected from published articles.ResultsGenetic diagnosis was established in 48.1% of patients, with WES identifying 57 pathogenic or likely pathogenic variants in 39.5% of cases. NOTCH3 and NOTCH2NLC were the most common mutated genes, accounting for 12.4% and 8.5% of cases, respectively. Dynamic mutation analysis revealed NOTCH2NLC GGC repeat expansions in 8.5% of patients. Different mutations resulted in varying clinical symptoms and imaging findings. Comparisons of genetic profiles between different populations showed distinct mutational spectrums in adult leukoencephalopathies.InterpretationThis study highlights the importance of genetic testing for accurate diagnosis and improved clinical management of these disorders. It also sheds light on the genetic heterogeneity of adult leukoencephalopathies across different races, emphasizing the need for further research on this topic.
Funder
Natural Science Foundation of Henan Province
National Natural Science Foundation of China
Subject
Neurology (clinical),General Neuroscience
Cited by
1 articles.
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