Skeletal muscle channelopathy

Gene: ATP1A2

Red List (low evidence)

The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 3:16 p.m. | Last Modified: 1 Feb 2023, 3:16 p.m.

Panel Version: 2.4

Red List (low evidence)

Comment on list classification: Leaving rating as Green but with a recommendation for review by GMS evaluation group as to suitability for this panel. There is only one case reported associated with a skeletal muscle phenotype.

Created: 8 Jun 2021, 5:30 p.m. | Last Modified: 20 Jul 2021, 1:55 p.m.

Panel Version: 1.31

Associated with Alternating hemiplegia of childhood 1 #104290 and Migraine, familial basilar/Migraine, familial hemiplegic, 2 #602481 in OMIM which are both CNS disorders.

PMID: 30423015 - Castaneda et al 2018 - report a 9 yo Brazilian boy with hypokalaemic periodic paralysis and CNS involvement, including seizures. He presented with episodes of flaccid muscle paralysis. A heterozygous de novo missense mutation (c.G2336A, p.S779N) in the ATP1A2 gene was identified using focussed exome sequencing. Electrophysiological studies in Xenopus oocytes of the p.S779N mutant pump showed an anomalous inward leak current and altered turnover rates. The authors postulate that this provides a mechanistic explanation for the periodic paralysis and CNS symptoms, respectively.

Other papers mentioned by James Polke
PMID: 15286158 - Bassi et al 2004 - report about alternating hemiplegia of childhood.
PMID: 18056581 - de Vries et al 2007 - report patients with hemiplegic migraine

A Pubmed search does not find any further cases of hypokalaemic periodic paralysis associated with ATP1A2

Created: 8 Jun 2021, 5:27 p.m. | Last Modified: 8 Jun 2021, 5:27 p.m.

Panel Version: 1.21

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
hypokalaemic periodic paralysis MONDO:0008223

Publications

• 30423015

Red List (low evidence)

Variants in this gene are predominantly linked to brain phenotypes such as alternating hemiplegia. Single report plus functional data linking to hypokalaemic periodic paralysis.

Created: 20 Aug 2020, 8:42 a.m. | Last Modified: 20 Aug 2020, 8:42 a.m.

Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypokalaemic periodic paralysis

Publications

• 30423015

I don't know

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 4:57 p.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Hypokalaemic periodic paralysis; Alternating hemiplegia of childhood 1, 104290; Migraine, familial hemiplegic, 2, 602481

Publications

• Castaneda et al 2018 Brain 141, 3308-3318 PMID: 30423015. Bassi et al 2004 J Med Genet 41, 621-8 PMID: 15286158. de Vries et al 2007 Neurology 69, 2170-6 PMID: 18056581

Variants in this GENE are reported as part of current diagnostic practice