Biallelic variants in PRORP is one of many causes for Perrault syndrome. Most affected individuals carry biallelic missense (hypomorphic) variants. These variants result in altered mitochondrial tRNA processing. All variants reported to date lie in the metallonuclease domain of PRORP. Mitochondrial respiratory chain complex I and IV deficiency is associated.
A single individual with a loss of function (frameshift) in trans with a missense variant has been reported with a more severe childhood onset metabolic disorder with developmental delay, lactic acidosis and hearing loss.
No individuals with two loss of function variants in PRORP have been described.
Genetic testing is available by targeted gene sequencing of PRORP or as analysis of exome or genome sequence data.
PRORP