Infantile Liver Failure Syndrome via the LARS1/LARS Gene

Infantile liver failure syndrome is a life-threatening condition characterized by recurrent episodes of acute liver failure in infancy or early childhood. Less frequently, acute infantile liver failure can be caused by defects in the LARS1/LARS gene. In addition to acute liver failure, phenotypes in patients with LARS1 deficiency includes anemia, renal tubulopathy, abnormal brain MRIs, failure to thrive, developmental delay, and seizures (Casey et al. 2012. PubMed ID: 22607940).

Infantile liver failure syndrome is an autosomal recessive disorder caused by defects in the NBAS gene or, much less frequently, in the LARS1 gene (Haack et al. 2015. PubMed ID: 26073778; Staufner et al. 2016. PubMed ID: 26541327; Casey et al. 2012. PubMed ID: 22607940).

The LARS1 gene (32 coding exons) encodes a cytoplasmic leucyl-tRNA synthetase enzyme, which catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu) during protein translation. So far, only missense variants in this gene have been reported in patients with infantile liver failure syndrome (Human Gene Mutation Database).

The pathogenic variant detection rate in the LARS1 gene in a large cohort of patients is unavailable because documented cases in the literature are limited (Casey et al. 2012. PubMed ID: 22607940). So far, no large deletions or duplications have been reported in the LARS1 gene.

This test provides full coverage of all coding exons of the LARS1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).