Clinical features and genetic analysis of two Chinese ATP1A2 gene variants pedigrees of familial hemiplegic migraine

Objective: To analyze the clinical manifestations and genetic examination results of affected members of two Chinese ATP1A2 gene variants pedigrees, and to summarize their phenotypic and genotypic features. Methods: The clinical features were recorded in detailed. The cranial magnetic resonance imaging for patients and gene sequencing of two Chinese ATP1A2 gene variant pedigrees were perform. The corre-lation between the types of variants and the clinical phenotypes of ATP1A2 gene were analyzed. Results: These two pedigrees are diagnosed as familial hemiplegic migraine type 2 (FHM2) with ATP1A2 heterozygous missense variants, c.1091C > T (p.T364M) found in pedigree 1 and c.899T > C (p.L300P) in pedigree 2. Multiple phenotypes coexist in both families, and the two probands have severe cranial magnetic resonance imaging manifesting hemiplegic contralateral cortical swelling and diffusion weighted imaging hyperintense signal, which can be fully recovered. ATP1A2 gene variants were seen in FHM2, sporadic hemiplegic migraine and atypical alternating hemiplegia of childhood (AHC) families or sporadic cases, etc. The clinical features of ATP1A2 variant c.1091C > T (p.T364M) are basically similar in Chinese patients and European patients. Conclusion: These two Chinese pedigrees had FHM2 due to ATP1A2 heterozygous missense variation. It would expand the understanding of ATP1A2.& COPY; 2023 Published by Elsevier Ltd on behalf of Tsinghua University Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).