AUTHOR=Yuan Jun-Hui , Higuchi Yujiro , Hashiguchi Akihiro , Ando Masahiro , Yoshimura Akiko , Nakamura Tomonori , Hiramatsu Yu , Sakiyama Yusuke , Takashima Hiroshi 

TITLE=Gene panel analysis of 119 index patients with suspected periodic paralysis in Japan

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1078195

DOI=10.3389/fneur.2023.1078195

ISSN=1664-2295

ABSTRACT=Genetic factors are recognized as major reason of patients with periodic paralysis. The goal of this study is to determine the genetic causes of periodic paralysis in Japan. We obtained a Japanese nationwide case series of 119 index patients (108 males and 11 females) clinically suspected with periodic paralysis, and a gene panel analysis, targeting CACNA1S, SCN4A, and KCNJ2 genes, was conducted. From 34 cases, 25 pathogenic/likely pathogenic/unknown significance variants were detected in CACNA1S (9 cases), SCN4A (19 cases), or KCNJ2 (6 cases), generating a molecular diagnostic rate of 28.6%. Seven variants have yet been found linked to periodic paralysis previously. The diagnostic yield of patients with hypokalemic and hyperkalemic periodic paralyses were 26.2% (17/65) and 32.7% (17/52), respectively. A considerably higher yield was procured from patients with than without positive family history (18/25 vs. 16/94), onset age <= 20 years (24/57 vs. 9/59), or recurrent paralytic attacks (31/94 vs. 3/25). The low molecular diagnostic rate and specific genetic proportion of the present study highlight the etiological complexity of patients with periodic paralysis in Japan.