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Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes
- Source :
- neurogenetics. 23:19-25
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Familial periodic paralyses (PPs) are inherited disorders of skeletal muscle characterized by recurrent episodes of flaccid muscle weakness. PPs are classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. HypoPP is an autosomal dominant disease caused by mutations in the CACNA1S gene, encoding for Cav1.1 channel (HypoPP-1), or SCN4A gene, encoding for Nav1.4 channel (HypoPP-2). In the present study, we included 60 patients with a clinical diagnosis of HypoPP. Fifty-one (85%) patients were tested using the direct sequencing (Sanger method) of all reported HypoPP mutations in CACNA1S and SCN4A genes; the remaining 9 (15%) patients were analyzed through a next-generation sequencing (NGS) panel, including the whole CACNA1S and SCN4A genes, plus other genes rarely associated to PPs. Fifty patients resulted mutated: 38 (76%) cases showed p.R528H and p.R1239G/H CACNA1S mutations and 12 (24%) displayed p.R669H, p.R672C/H, p.R1132G/Q, and p.R1135H SCN4A mutations. Forty-one mutated cases were identified among the 51 patients managed with Sanger sequencing, while all the 9 cases directly analyzed with the NGS panel showed mutations in the hotspot regions of SCN4A and CACNA1S. Ten out of the 51 patients unresolved through the Sanger sequencing were further analyzed with the NGS panel, without the detection of any mutation. Hence, our data suggest that in HypoPP patients, the extension of genetic analysis from the hotspot regions using the Sanger method to the NGS sequencing of the entire CACNA1S and SCN4A genes does not lead to the identification of new pathological mutations.
- Subjects :
- Calcium Channels, L-Type
Biology
medicine.disease_cause
Genetic analysis
DNA sequencing
Cellular and Molecular Neuroscience
symbols.namesake
Hypokalemic periodic paralysis
Genetics
medicine
Humans
Genetic Testing
NAV1.4 Voltage-Gated Sodium Channel
Muscle, Skeletal
Gene
Genetics (clinical)
Sanger sequencing
Mutation
Massive parallel sequencing
Autosomal dominant trait
Sanger method
CACNA1S and SCN4A genes
medicine.disease
Next-generation sequencing
symbols
Subjects
Details
- ISSN :
- 13646753 and 13646745
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- neurogenetics
- Accession number :
- edsair.doi.dedup.....a894506cc5ceea2f68436140998646e5