Short QT syndrome

Gene: SLC22A5

The 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

• 10545605
• 11261427

Green List (high evidence)

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

• 26190315
• 29198778
• 31472821

Red List (low evidence)

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

Red List (low evidence)

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

• 26190315

Red List (low evidence)

Carnitine deficiency, systemic primary 212140

Created: 25 Mar 2019, 4:30 p.m.

Not associated with SQT

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

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.

I don't know

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.

Green List (high evidence)

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: Literature

Created: 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

• PMID: 7254270
• 7131143
• 26190315
• 29198778