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=14

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=<sec><title>Introduction</title><p>Genetic factors are recognized as the major reason for patients with periodic paralysis. The goal of this study was to determine the genetic causes of periodic paralysis in Japan.</p></sec><sec><title>Methods</title><p>We obtained a Japanese nationwide case series of 119 index patients (108 men and 11 women) clinically suspected of periodic paralysis, and a gene panel analysis, targeting <italic>CACNA1S, SCN4A</italic>, and <italic>KCNJ2</italic> genes, was conducted.</p></sec><sec><title>Results</title><p>From 34 cases, 25 pathogenic/likely pathogenic/unknown significance variants were detected in <italic>CACNA1S</italic> (nine cases), <italic>SCN4A</italic> (19 cases), or <italic>KCNJ2</italic> (six cases), generating a molecular diagnostic rate of 28.6%. In total, seven variants have yet been found linked to periodic paralysis previously. The diagnostic yield of patients with hypokalemic and hyperkalemic periodic paralyzes was 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).</p></sec><sec><title>Discussion</title><p>The low molecular diagnostic rate and specific genetic proportion of the present study highlight the etiological complexity of patients with periodic paralysis in Japan.</p></sec>