Early onset or syndromic epilepsy

Gene: LARS

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

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

Added new-gene-name tag, new approved HGNC gene symbol for LARS is LARS1

Created: 8 Dec 2020, 10:28 a.m. | Last Modified: 8 Dec 2020, 10:28 a.m.

Panel Version: 2.233

Comment on list classification: New gene added by Konstantinos Varvagiannis. Seizures are prevalent among affected individuals, often triggered by infections. There is sufficient evidence for this gene to be rated GREEN at the next major review and depending on the policy of inclusion of metabolic genes on this panel (added 'for-review tag).

Created: 8 Dec 2020, 10:27 a.m. | Last Modified: 8 Dec 2020, 10:27 a.m.

Panel Version: 2.233

Green List (high evidence)

Please consider inclusion with amber/green rating in the current panel.

Biallelic pathogenic LARS1 variants cause Infantile liver failure syndrome 1, MIM# 615438.

Lenz et al (2020 - PMID: 32699352) review the phenotype of 25 affected individuals from 15 families.

Seizures occurred in 19/24 and were commonly associated with infections. Encephalopathic episodes (in 13 patients) accompanied by seizures up to status epilepticus occurred independently of hepatic decompensation.

In addition 22/24 presented with neurodevelopmental delay. The authors comment that cognitive impairment was present in 13/17 individuals (mild-severe) whereas most presented with learning disabilities.

These patients will be most likely investigated for their liver disease (although presentation was highly variable and/or very mild in few).

The gene encodes a cytoplasmic amino-acyl tRNA synthetase (ARS) with neurologic manifestations observed in almost all patients (and seizures / DD and ID common to other disorders due to mutations in other genes encoding for ARSs).

Please note that the HGNC approved symbol for this gene is LARS1.
Sources: Literature

Created: 27 Jul 2020, 9:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile liver failure syndrome 1, MIM# 615438

Publications

• 32699352