Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype.

ABSTRACT:

Background

Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to its cognate transfer RNA and therefore plays an essential role in protein biosynthesis.

Methods

We used exome sequencing, aminoacylation assays, homology modeling, and immuno-isolation of transfected MARS to identify and characterize mutations in the methionyl-tRNA synthetase gene (MARS) in an infant with an unexplained multi-organ phenotype.

Results

We identified compound heterozygous mutations (F370L and I523T) in highly conserved regions of MARS. The parents were each heterozygous for one of the mutations. Aminoacylation assays documented that the F370L and I523T MARS mutants had 18 ± 6% and 16 ± 6%, respectively, of wild-type activity. Homology modeling of the human MARS sequence w

SUBMITTER: van Meel E 

PROVIDER: S-EPMC3852179 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature