Skeletal muscle channelopathy
Gene: ATP1A2
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
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 ATP1A2Created: 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
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
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.
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
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: ATP1A2. Tag Q2_21_phenotype was removed from gene: ATP1A2. Tag Q2_21_expert_review was removed from gene: ATP1A2.
Source Expert Review Red was added to ATP1A2. Rating Changed from Green List (high evidence) to Red List (low evidence)
Tag Q2_21_rating tag was added to gene: ATP1A2. Tag Q2_21_expert_review tag was added to gene: ATP1A2.
Tag Q2_21_rating was removed from gene: ATP1A2.
Tag Q2_21_phenotype tag was added to gene: ATP1A2.
Gene: atp1a2 has been classified as Green List (High Evidence).
Tag Q2_21_rating tag was added to gene: ATP1A2.
Phenotypes for gene: ATP1A2 were changed from Migraine, familial hemiplegic, 2, 602481; Alternating hemiplegia of childhood 1, 104290; Hypokalaemic periodic paralysis to hypokalaemic periodic paralysis MONDO:0008223
Publications for gene: ATP1A2 were set to 30423015; 15286158; 18056581
Publications for gene ATP1A2 were changed from to 30423015; 15286158; 18056581
Mode of inheritance for gene ATP1A2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Migraine, familial hemiplegic, 2, 602481; Alternating hemiplegia of childhood 1, 104290; Hypokalaemic periodic paralysis for gene: ATP1A2
Source Expert Review Green was added to ATP1A2. Rating Changed from Red List (low evidence) to Green List (high evidence)
Source NHS GMS was added to ATP1A2.
gene: ATP1A2 was added gene: ATP1A2 was added to Myotonia congenita. Sources: London North GLH Mode of inheritance for gene: ATP1A2 was set to