AUTHOR=Li Yinchao , Liu Xianyue , Wang Chengzhe , Su Zhengwei , Zhao Ke , Yang Man , Chen Shuda , Zhou Liemin 

TITLE=Molecular and clinical characteristics of ATP1A3-related diseases

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.924788

DOI=10.3389/fneur.2022.924788

ISSN=1664-2295

ABSTRACT=<sec><title>Objective</title><p>With detailed studies of <italic>ATP1A3</italic>-related diseases, the phenotypic spectrum of <italic>ATP1A3</italic> has greatly expanded. This study aimed to potentially identify the mechanisms by which <italic>ATP1A3</italic> caused neurological dysfunction by analyzing the clinical features and phenotypes of <italic>ATP1A3</italic>-related diseases, and exploring the distribution patterns of mutations in the subregions of the <italic>ATP1A3</italic> protein, thus providing new and effective therapeutic approaches.</p></sec><sec><title>Methods</title><p>Databases of PubMed, Online Mendelian Inheritance in Man, and Human Gene Mutation Database, Wanfang Data, and Embase were searched for case reports of <italic>ATP1A3</italic>-related diseases. Following case screening, we collected clinical information and genetic testing results of patients, and analyzed the disease characteristics on the clinical phenotype spectrum associated with mutations, genetic characteristics of mutations, and effects of drug therapy.</p></sec><sec><title>Results</title><p>We collected 902 clinical cases related to <italic>ATP1A3</italic> gene. From the results of previous studies, we further clarified the clinical characteristics of <italic>ATP1A3-</italic>related diseases, such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism; cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome, and relapsing encephalopathy with cerebellar ataxia, frequency of mutations in different phenotypes and their distribution in gene and protein structures, and differences in mutations in different clinical phenotypes. Regarding the efficacy of drug treatment, 80 of the 124 patients with AHC were treated with flunarizine, with an effectiveness rate of ~64.5%.</p></sec><sec><title>Conclusions</title><p>Nervous system dysfunction due to mutations of <italic>ATP1A3 gene</italic> was characterized by a group of genotypic–phenotypic interrelated disease pedigrees with multiple clinical manifestations. The presented results might help guide the diagnosis and treatment of <italic>ATP1A3</italic>-related diseases and provided new ideas for further exploring the mechanisms of nervous system diseases due to <italic>ATP1A3</italic> mutations.</p></sec>