De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations
Abstract 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 characteristi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-03-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1874 |
| _version_ | 1818532660801175552 |
|---|---|
| author | Tangfeng Su Yu Yan Qingqing Hu Yan Liu Sanqing Xu |
| author_facet | Tangfeng Su Yu Yan Qingqing Hu Yan Liu Sanqing Xu |
| author_sort | Tangfeng Su |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-11T17:48:26Z |
| format | Article |
| id | doaj.art-ab981bc5a0af4fed823872f10bb71eb7 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-11T17:48:26Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-ab981bc5a0af4fed823872f10bb71eb72022-12-22T00:56:17ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-03-01103n/an/a10.1002/mgg3.1874De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformationsTangfeng Su0Yu Yan1Qingqing Hu2Yan Liu3Sanqing Xu4Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology People's Hospital of Dongxihu District Wuhan ChinaDepartment of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract 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.https://doi.org/10.1002/mgg3.1874developmental and epileptic encephalopathydynein cytoplasmic 1 heavy chain 1epileptic spasmsketogenic dietvagus nerve stimulation |
| spellingShingle | Tangfeng Su Yu Yan Qingqing Hu Yan Liu Sanqing Xu De novo DYNC1H1 mutation causes infantile developmental and epileptic encephalopathy with brain malformations Molecular Genetics & Genomic Medicine developmental and epileptic encephalopathy dynein cytoplasmic 1 heavy chain 1 epileptic spasms ketogenic diet vagus nerve stimulation |
| 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 | developmental and epileptic encephalopathy dynein cytoplasmic 1 heavy chain 1 epileptic spasms ketogenic diet vagus nerve stimulation |
| url | https://doi.org/10.1002/mgg3.1874 |
| work_keys_str_mv | AT tangfengsu denovodync1h1mutationcausesinfantiledevelopmentalandepilepticencephalopathywithbrainmalformations AT yuyan denovodync1h1mutationcausesinfantiledevelopmentalandepilepticencephalopathywithbrainmalformations AT qingqinghu denovodync1h1mutationcausesinfantiledevelopmentalandepilepticencephalopathywithbrainmalformations AT yanliu denovodync1h1mutationcausesinfantiledevelopmentalandepilepticencephalopathywithbrainmalformations AT sanqingxu denovodync1h1mutationcausesinfantiledevelopmentalandepilepticencephalopathywithbrainmalformations |