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De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations

BACKGROUND: The human dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene encodes a large subunit of the cytoplasmic dynein complex. DYNC1H1 mutations are associated with various neurological diseases involving both the peripheral and central nervous systems. METHODS: The clinical characteristics and...

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Autores principales: Su, Tangfeng, Yan, Yu, Hu, Qingqing, Liu, Yan, Xu, Sanqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922968/
https://www.ncbi.nlm.nih.gov/pubmed/35099838
http://dx.doi.org/10.1002/mgg3.1874
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author Su, Tangfeng
Yan, Yu
Hu, Qingqing
Liu, Yan
Xu, Sanqing
author_facet Su, Tangfeng
Yan, Yu
Hu, Qingqing
Liu, Yan
Xu, Sanqing
author_sort Su, Tangfeng
collection PubMed
description BACKGROUND: The human dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene encodes a large subunit of the cytoplasmic dynein complex. DYNC1H1 mutations are associated with various neurological diseases involving both the peripheral and central nervous systems. METHODS: The clinical characteristics and genetic data of an infant carrying the de novo DYNC1H1 variant identified by trio exome sequencing were analyzed. Patients with epilepsy with DYNC1H1 mutations were summarized by reviewing the literature. RESULTS: We first identified an infant presenting with epileptic spasms harboring a de novo missense mutation in DYNC1H1 (c.874C>T; p. Arg292Trp), once reported in an adult case, and further summarized another 54 patients with seizures or epilepsy caused by DYNC1H1 pathogenic variants in the literature. Refractory epilepsy, intellectual disability, and cortical developmental malformations are crucial characteristics of patients with developmental and epileptic encephalopathy (DEE) caused by DYNC1H1 variants. Notably, epileptic spasms in this case were resistant to multiple anti‐seizure medications, corticosteroids, ketogenic diet, and vagus nerve stimulation treatment. The child also showed cortical gyrus malformation and global developmental delay. CONCLUSION: DYNC1H1 variants can cause infantile developmental and epileptic encephalopathy, in which Arg292Trp is a mutation hotspot of the DYNC1H1 gene. Epileptic seizures in this type of DYNC1H1‐related DEE are mostly resistant to multiple antiepileptic strategies and need to explore optimized treatments.
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spelling pubmed-89229682022-03-21 De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations Su, Tangfeng Yan, Yu Hu, Qingqing Liu, Yan Xu, Sanqing Mol Genet Genomic Med Original Articles BACKGROUND: The human dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene encodes a large subunit of the cytoplasmic dynein complex. DYNC1H1 mutations are associated with various neurological diseases involving both the peripheral and central nervous systems. METHODS: The clinical characteristics and genetic data of an infant carrying the de novo DYNC1H1 variant identified by trio exome sequencing were analyzed. Patients with epilepsy with DYNC1H1 mutations were summarized by reviewing the literature. RESULTS: We first identified an infant presenting with epileptic spasms harboring a de novo missense mutation in DYNC1H1 (c.874C>T; p. Arg292Trp), once reported in an adult case, and further summarized another 54 patients with seizures or epilepsy caused by DYNC1H1 pathogenic variants in the literature. Refractory epilepsy, intellectual disability, and cortical developmental malformations are crucial characteristics of patients with developmental and epileptic encephalopathy (DEE) caused by DYNC1H1 variants. Notably, epileptic spasms in this case were resistant to multiple anti‐seizure medications, corticosteroids, ketogenic diet, and vagus nerve stimulation treatment. The child also showed cortical gyrus malformation and global developmental delay. CONCLUSION: DYNC1H1 variants can cause infantile developmental and epileptic encephalopathy, in which Arg292Trp is a mutation hotspot of the DYNC1H1 gene. Epileptic seizures in this type of DYNC1H1‐related DEE are mostly resistant to multiple antiepileptic strategies and need to explore optimized treatments. Blackwell Publishing Ltd 2022-01-31 /pmc/articles/PMC8922968/ /pubmed/35099838 http://dx.doi.org/10.1002/mgg3.1874 Text en © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Su, Tangfeng
Yan, Yu
Hu, Qingqing
Liu, Yan
Xu, Sanqing
De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
title De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
title_full De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
title_fullStr De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
title_full_unstemmed De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
title_short De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
title_sort de novo dync1h1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922968/
https://www.ncbi.nlm.nih.gov/pubmed/35099838
http://dx.doi.org/10.1002/mgg3.1874
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