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New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies

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 st...

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Autores principales: Xie, Juan‐Juan, Ni, Wang, Wei, Qiao, Ma, Huan, Bai, Ge, Shen, Ying, Wu, Zhi‐Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163788/
https://www.ncbi.nlm.nih.gov/pubmed/31885218
http://dx.doi.org/10.1111/cns.13284
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author Xie, Juan‐Juan
Ni, Wang
Wei, Qiao
Ma, Huan
Bai, Ge
Shen, Ying
Wu, Zhi‐Ying
author_facet Xie, Juan‐Juan
Ni, Wang
Wei, Qiao
Ma, Huan
Bai, Ge
Shen, Ying
Wu, Zhi‐Ying
author_sort Xie, Juan‐Juan
collection PubMed
description 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.
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spelling pubmed-71637882020-04-20 New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies Xie, Juan‐Juan Ni, Wang Wei, Qiao Ma, Huan Bai, Ge Shen, Ying Wu, Zhi‐Ying CNS Neurosci Ther Original Articles 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. John Wiley and Sons Inc. 2019-12-29 /pmc/articles/PMC7163788/ /pubmed/31885218 http://dx.doi.org/10.1111/cns.13284 Text en © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xie, Juan‐Juan
Ni, Wang
Wei, Qiao
Ma, Huan
Bai, Ge
Shen, Ying
Wu, Zhi‐Ying
New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
title New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
title_full New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
title_fullStr New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
title_full_unstemmed New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
title_short New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
title_sort new clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163788/
https://www.ncbi.nlm.nih.gov/pubmed/31885218
http://dx.doi.org/10.1111/cns.13284
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