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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2024

Open Access 01-12-2024 | Periodic Paralysis | Research

Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients

Authors: Xuechao Zhao, Haofeng Ning, Lina Liu, Chaofeng Zhu, Yinghui Zhang, Guifang Sun, Huanan Ren, Xiangdong Kong

Published in: Orphanet Journal of Rare Diseases | Issue 1/2024

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Abstract

Background

Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population.

Results

We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants.

Conclusions

Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.
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Metadata
Title
Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients
Authors
Xuechao Zhao
Haofeng Ning
Lina Liu
Chaofeng Zhu
Yinghui Zhang
Guifang Sun
Huanan Ren
Xiangdong Kong
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2024
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-024-03170-5

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