Clinical and genetic analyses of ATP1A2 gene-related childhood neurological diseases
10.3760/cma.j.cn115354-20250424-00242
- VernacularTitle:ATP1A2基因相关儿童神经系统疾病的临床及遗传学分析
- Author:
Zhen ZHOU
1
;
Sai YANG
;
Zeshu NING
;
Bo CHEN
;
Shuju ZHANG
;
Liwen WU
Author Information
1. 中南大学湘雅医学院附属儿童医院（湖南省儿童医院）神经内科，长沙 410007
- Publication Type:Journal Article
- Keywords:
ATP1A2 gene;
Hemiplegic migraine;
Epilepsy;
Acute encephalopathy;
Clinical phenotype;
Genetic mutation
- From:
Chinese Journal of Neuromedicine
2025;24(7):680-688
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.
