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

Molecular Genetics & Genomic Medicine

Yu Yan¹  Tangfeng Su²  Sanqing Xu²  Yan Liu²  Qingqing Hu² 

[1] Department of Neurology People's Hospital of Dongxihu District Wuhan China;Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China;

关键词: developmental and epileptic encephalopathy;    dynein cytoplasmic 1 heavy chain 1;    epileptic spasms;    ketogenic diet;    vagus nerve stimulation;   

DOI  :  10.1002/mgg3.1874

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown