Open AccessNew clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
Author(s) -
Xie JuanJuan,
Ni Wang,
Wei Qiao,
Ma Huan,
Bai Ge,
Shen Ying,
Wu ZhiYing
Publication year - 2020
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13284
Subject(s) - proband , nonsense , medical genetics , missense mutation , exome sequencing , medicine , genetics , genetic testing , bioinformatics , biology , mutation , gene
Abstract Aim Leukodystrophies are a group of inherited white matter disorders with clinical, genetic, and imaging heterogeneity, which usually pose a diagnostic challenge for physicians. We aimed to identify new clinical characteristics and novel pathogenic variants of hereditary leukodystrophies in this study. Methods Whole exome sequencing (WES) was performed in 28 unrelated patients clinically suspected with leukodystrophies. Leukocytes enzyme activity test, electroencephalogram (EEG), electromyography (EMG), and brain MRI were conducted. Functional analysis was performed, and the pathogenicity of variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Results We made definite diagnosis in 8 probands with 12 pathogenic variants and reported new clinical characteristics and imaging features of these patients. Three novel pathogenic variants were identified, including a microdeletion variant c.2654_2654+3del within CSF1R , a nonsense variant c.1321C>T, and a missense variant c.166G>C within GALC . Conclusion Our results have deepened the understanding of clinical, genetic, and imaging heterogeneity of hereditary leukodystrophies, and expanded the spectrum of pathogenic variants and clinical features.