Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype.
BMC Med Genet
; 14: 106, 2013 Oct 08.
Article
en En
| MEDLINE
| ID: mdl-24103465
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 with the structure of E. coli MARS showed that the F370L and I523T mutations are in close proximity to each other, with residue I523 located in the methionine binding pocket. We found that the F370L and I523T mutations did not affect the association of MARS with the multisynthetase complex. CONCLUSION: This infant expands the catalogue of inherited human diseases caused by mutations in aminoacyl-tRNA synthetase genes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metionina-ARNt Ligasa
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
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Infant
Idioma:
En
Revista:
BMC Med Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido