Molecular characteristics

LARS2 is a mitochondrial aminoacylsynthetase which attaches leucine to the appropriate mitochondrial transfer RNA (tRNA). Studies indicate that disturbances of mitochondrial translation are the cause of LARS2-related disorders.

Perrault syndrome
LARS2-associated Perrault syndrome is caused by homozygous and compound heterozygous hypomorphic missense variants. One individual was reported with a frameshift variant in trans to a missense variant. LARS2 c.1565C>A in either the homozygous state or in a heterozygous state in trans to another pathogenic LARS2 variant is associated with low frequency sensorineural hearing loss.

Lethal infantile multisystem failure
In the single reported individual the condition was due to compound heterozygous hypomorphic and deleterious missense variants. One of the variants in the individual is associated with Perrault syndrome. This variant in combination with the more deleterious variant produced the more severe phenotype in the infant.