title: No Evidence for Mutations that Deregulate GARS-AIRS-GART Protein Levels in Children with Down Syndrome.
abstract: GARS-AIRS-GART is crucial in studies of Down syndrome (DS)-related mental retardation due to its chromosomal location (21q22.1), involvement in de novo purine biosynthesis and over-expression in fetal DS brain postmortem samples. GARS-AIRS-GART regions important for structure-function were screened for mutations that might alter protein levels in DS patients. Mutation screening relied on multiplex/singleplex PCR-based amplification of genomic targets followed by amplicon size determination/fingerprinting. Serum protein samples were resolved by SDS-PAGE and immunoblotted with a GARS-AIRS-GART monoclonal antibody. No variation in amplicon size/fingerprints was observed in regions encoding the ATP-binding, active site residues of GARS, the structurally important glycine-rich loops of AIRS, substrate-binding, flexible and folate-binding loops of GART or the poly-adenylation signal sequences. The de novo occurrence or inheritance of large insertion/deletion/rearrangement-type mutations is therefore excluded. Immunoblots show presence of GARS-AIRS-GART protein in all patient samples, with no change in expression levels with respect to either sex or developmental age.
  
  
  BACKGROUND
  The online version of this article (doi:10.1007/s12291-011-0183-6) contains supplementary material, which is available to authorized users.
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482 Madudah, Plot I-24, Sector J, Eastern Metropolitan Bypass, Kolkata, 700 107 India.
authors.forename: Disha
authors.initials: D
authors.lastname: Banerjee
authors.forename: Debarati
authors.initials: D
authors.lastname: Ghosh
authors.forename: Anindita
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.forename: Krishnadas
authors.initials: K
authors.lastname: Nandagopal
keywords: Down syndrome-related mental retardation; GARS–AIRS–GART; Immunoblot; Mutation screen; Survival