Short QT syndrome
Gene: SLC22A5The mode of inheritance for SLC22A5 variants should be BIALLELIC, autosomal or pseudoautosomal. Although, heterozygous SLC22A5 variants have been seen in a few cases, these are detectable biochemically and are not associated with clear clinical presentation (PMID: 10545605; 11261427).Created: 1 Aug 2023, 1:56 p.m. | Last Modified: 8 Aug 2023, 9:38 a.m.
Panel Version: 3.6
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Some evidence (published and anecdotal) to suggest causative role in SQTS in the context of primary carnitine deficiency (including in the absence of heart muscle disease).Created: 27 Nov 2019, 12:17 p.m. | Last Modified: 27 Nov 2019, 12:17 p.m.
Panel Version: 1.23
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Comment on list classification: Demoted from Green to Red as the GMS Cardiology specialist group feels that this gene should not be on this panel.Created: 27 Nov 2019, 1:10 p.m. | Last Modified: 27 Nov 2019, 1:10 p.m.
Panel Version: 1.24
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.Created: 18 Nov 2019, 2:46 p.m. | Last Modified: 18 Nov 2019, 2:46 p.m.
Panel Version: 1.23
Comment on mode of inheritance: Phenotype changed due to expert reviews.Created: 30 Sep 2019, 12:24 p.m. | Last Modified: 30 Sep 2019, 12:24 p.m.
Panel Version: 1.21
Literature associates with SQTS secondary to carnitine deficiency.Created: 27 Sep 2019, 1:56 p.m. | Last Modified: 27 Sep 2019, 1:56 p.m.
Panel Version: 1.20
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Carnitine deficiency, systemic primary 212140
Publications
Carnitine deficiency, systemic primary 212140Created: 25 Mar 2019, 4:30 p.m.
Not associated with SQTCreated: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.Created: 20 Feb 2019, 2:17 p.m.
Mutations in this gene cause carnitine definciency. Clinical characteristics are primarily hepatic and cerebral dysfunction lethargy and hypoglycaemia. Cardiomyopathy is also a feature. No evidence that mutations in this gene cause primary or isolated Short QT syndrome.Created: 25 Jan 2019, 12:52 p.m.
SLC22A5 loss of function mutations lead to defective OCTN2, which leads to primary carnitine deficiency.
PCD has been recognised for a long time. Autosomal recessive, although some heterozygotes can display symptoms. PCD impairs carnitine uptake into cardiac myocytes, leads to impaired long chain fatty acid uptake into mitochondria. It leads to a cardiomyopathy (dilated) and there is an association with arrhytomogenesis. There is now good evidence that PCD produces a short QT phenoype in humans and in an animal model, though the precise mechanism is unknown. It is important to include SLC22A5 screening on a panel for SQTS, particularly where there is evidence for cardiomyopathy, because when it is identified it can be treated with dietary L-carnitine supplementation.
Additional case report: https://www.hindawi.com/journals/cric/2018/3232105/
Sources: LiteratureCreated: 17 Oct 2018, 9:47 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency
Publications
Mode of inheritance for gene: SLC22A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: SLC22A5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SLC22A5 were changed from arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency; Carnitine deficiency, systemic primary 212140 to Carnitine deficiency, systemic primary, OMIM:212140; systemic primary carnitine deficiency disease, MONDO:0008919
Publications for gene: SLC22A5 were set to 7254270; 7131143; 26190315; 29198778
Mode of inheritance for gene: SLC22A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Gene: slc22a5 has been classified as Red List (Low Evidence).
Mode of inheritance for gene: SLC22A5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source West Midlands, Oxford and Wessex GLH was added to SLC22A5.
Source South West GLH was added to SLC22A5. Mode of inheritance for gene SLC22A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Source London South GLH was added to SLC22A5.
Jules Hancox: SLC22A5 loss of function mutat
Phenotypes for gene: SLC22A5 were changed from arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency to arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency; Carnitine deficiency, systemic primary 212140
Publications for gene: SLC22A5 were set to PMID: 7254270; 7131143; 26190315; 29198778
Source Expert Review Green was added to SLC22A5. Mode of inheritance for gene SLC22A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Rating Changed from No List (delete) to Green List (high evidence)
gene: SLC22A5 was added gene: SLC22A5 was added to Short QT syndrome. Sources: Literature Mode of inheritance for gene: SLC22A5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC22A5 were set to PMID: 7254270; 7131143; 26190315; 29198778 Phenotypes for gene: SLC22A5 were set to arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency Review for gene: SLC22A5 was set to GREEN