Biallelic mutations of the methionyl-tRNA synthetase (MARS) cause a specific type of pulmonary alveolar proteinosis prevalent on Réunion Island

Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to tRNA and is critical for protein biosynthesis. We identified biallelic missense mutations in MARS in a specific form of pediatric pulmonary alveolar proteinosis (PAP), a severe lung disorder which is prevalent on the Island of Réunion and whose molecular basis is unresolved. Mutations were found in 26 individuals from Réunion and nearby islands and 2 families from other countries. Functional consequences of the mutated alleles were assessed by growth and methionine incorporation assays in yeast. Enzyme activity was attenuated in liquid medium without methionine, but could be restored by methionine supplementation. In summary, identification of a founder mutation in MARS led to the molecular definition of a specific type of PAP and will enable carrier screening in the affected community and possibly opens new treatment opportunities.