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

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

doi:10.3389/fneur.2023.1078195

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

Front Neurol. 2023 Jan 26:14:1078195. doi: 10.3389/fneur.2023.1078195. eCollection 2023.

Authors

Jun-Hui Yuan¹, Yujiro Higuchi¹, Akihiro Hashiguchi¹, Masahiro Ando¹, Akiko Yoshimura¹, Tomonori Nakamura¹, Yu Hiramatsu¹, Yusuke Sakiyama¹, Hiroshi Takashima¹

Affiliation

¹ Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Abstract

Introduction: 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.

Methods: 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 CACNA1S, SCN4A, and KCNJ2 genes, was conducted.

Results: From 34 cases, 25 pathogenic/likely pathogenic/unknown significance variants were detected in CACNA1S (nine cases), SCN4A (19 cases), or KCNJ2 (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).

Discussion: The low molecular diagnostic rate and specific genetic proportion of the present study highlight the etiological complexity of patients with periodic paralysis in Japan.

Keywords: CACNA1S; KCNJ2; SCN4A; gene panel sequencing; periodic paralysis.

Grants and funding

This work was supported by the grants-in-aid from the Research Committee of Ataxia, Health Labor Sciences Research Grant, the Ministry of Health, Labor and Welfare, Japan (20317603 and 201610002B). This research was also supported by the research program for conquering intractable disease from the Japan Agency for Medical Research and Development (AMED) (201442014A and 201442071A) and JSPS KAKENHI Grants (JP18H02742, JP20K16604, JP21K15702, JP21H02842, JP22K07495, and JP22K15713).