Hypokalemic periodic paralysis and mutations in the <i>CACNL1A3</i> gene: Case study in a Japanese family

Wada, Taizo; Yachie, Akihiro; Fujita, Shuhei; Takei, Kenkichi; Sumita, Ryo; Ichihara, Tomofumi; Koizumi, Shoichi

doi:10.1046/j.1442-200x.2000.01214.x

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…The second search yielded 720 articles and provided 5 additional HypoPP family or cohort studies with brief reports on cardiac arrhythmia (Fig. ) . The 16 articles from both searches described 25 HypoPP patients with cardiac arrhythmia (Table ).…”

Section: Resultsmentioning

confidence: 99%

Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?

Stunnenberg

Deinum

Links³

et al. 2014

Muscle and Nerve

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It is unknown how often cardiac arrhythmias occur in hypokalemic periodic paralysis (HypoPP) and if they are caused by hypokalemia alone or other factors. This systematic review shows that cardiac arrhythmias were reported in 27 HypoPP patients. Cases were confirmed genetically (13 with an R528H mutation in CACNA1S, 1 an R669H mutation in SCN4A) or had a convincing clinical diagnosis of HypoPP (13 genetically undetermined) if reported prior to the availability of genetic testing. Arrhythmias occurred during severe hypokalemia (11 patients), between attacks at normokalemia (4 patients), were treatment-dependent (2 patients), or unspecified (10 patients). Nine patients died from arrhythmia. Convincing evidence for a pro-arrhythmogenic factor other than hypokalemia is still lacking. The role of cardiac expression of defective skeletal muscle channels in the heart of HypoPP patients remains unclear. Clinicians should be aware of and prevent treatment-induced cardiac arrhythmia in HypoPP.

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Section: Resultsmentioning

confidence: 99%

Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?

Stunnenberg

Deinum

Links³

et al. 2014

Muscle and Nerve

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“…The arginine to histidine substitution at position 528 (p.Arg528His, NC_000001.11:g.201077915C>T, rs80338777) was reported in multiple case and family studies [6,[58][59][60][61][62][63][64][65][66][67][68][69][70][71] and also as de-novo mutation [61]. Although, HypoPP1 is inherited as an autosomal dominant trait, penetrance in males is much higher than in females.…”

Section: Parg528his (Rs80338777c>t)mentioning

confidence: 99%

PharmGKB summary: very important pharmacogene information for CACNA1S

Sangkuhl

Dirksen

Alvarellos

et al. 2020

Pharmacogenetics and Genomics

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The CACNA1S gene encodes the α1s subunit of the dihydropyridine receptor (DHPR), a voltagegated calcium channel and voltage sensor for Ca 2+ release in skeletal muscle. Variants in the CACNA1S gene have been linked to the pharmacogenetic disorder known as malignant hyperthermia susceptibility (MHS) and hypokalemic periodic paralysis (hypoPP). Two variants in CACNA1S are verified by the European Malignant Hyperthermia Group (EMHG) to be associated with MHS [1]. Although the occurrence of MHS during anesthesia is relatively rare, the genetic prevalence of MHS-causative mutations is estimated to be between 1 in 400 [2] to 1 in 2000-3000 [3]. The American College of Medical Genetics (ACMG) "Guidelines for Reporting Incidental Findings in Clinical Exome and Genome Sequencing" includes "known pathogenic" and "likely pathogenic" variants in CACNA1S related to MHS in its list of genetic variants to report as incidental findings [4,5]. In addition, 9 CACNA1S variants are linked to hypoPP [6]. Finally, several CACNA1S variants and polymorphisms are proposed to be associated with thyrotoxic periodic paralysis (TPP) [7], hyperCKemia [8] and statin-associated myopathy [9]. Thus, the CACNA1S gene is associated with an eclectic array of muscle disorders with clinical manifestations ranging from subclinical myopathies, episodic paralysis, and life-threatening response to anesthesia.

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“…To date, eight missense mutations have been identified in association with HypoPP. Mutations in the calcium channel gene, CACNA1S , on chromosome 1q31‐q32 (Arg528His, Arg1239His, and Arg1239Gly2, 7, 14), lead to HypoPP type 1 and account for 70% of HypoPP cases 9, 10, 27, 30, 32. Four mutations in the sodium channel gene, SCN4A , on chromosome 17q23.1‐q25.3, lead to type 2 cases (Arg669His, Arg672His, Arg672Gly, and Arg672Ser3, 5, 11, 28).…”

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confidence: 99%

Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia

et al. 2004

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Hypokalemic periodic paralysis (HypoPP) and malignant hyperthermia (MH) are autosomal-dominant genetically heterogeneous ion channelopathies. MH has been described in patients with HypoPP, suggesting a potential link between these disorders. However, a common genetic determinant has not been described. With the aim of corroborating this association, four candidate genes were screened in two independent HypoPP patients, one of whom was also diagnosed as MH-susceptible and the other as MH-normal by the in vitro contracture test (IVCT). An A>G change at nucleotide 7025 was detected in the RYR1 gene in the HypoPP/MH-susceptible patient. Detection of the same mutation in three independent MH families suggested that 7025A>G represents a novel MH-susceptibility allele and that MH and HypoPP occurred independently in the case presented. Conclusive evidence in support of the hypothesis that MH and HypoPP are allelic was therefore not obtained.

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Hypokalemic periodic paralysis and mutations in the CACNL1A3 gene: Case study in a Japanese family

Cited by 4 publications

References 10 publications

Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?

Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?

PharmGKB summary: very important pharmacogene information for CACNA1S

Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia

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