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A novel nonstop mutation in TYMP does not induce nonstop mRNA decay in a MNGIE patient with severe neuropathy
Author(s) -
TorresTorronteras Javier,
RodriguezPalmero Agustí,
Pinós Tomàs,
Accarino Anna,
Andreu Antoni L.,
PintosMorell Guillem,
Martíí Ramon
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21447
Subject(s) - nonstop , nonsense mediated decay , biology , genetics , thymidine phosphorylase , gene , rna , computer science , cancer , rna splicing , operating system
The cellular quality control systems enable surveillance and selective degradation of nonsense, nonstop, and no‐go mRNAs. In the case of nonstop mRNA, different mechanisms of nonstop‐mediated decay (NSD) have been described for bacteria, yeast and mammals, but the molecular consequences of nonstop mutations have been examined in only few cases of human disease. We describe a novel homozygous nonstop mRNA mutation (c.1416delC) in the TYMP gene encoding thymidine phosphorylase, in a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). In contrast to previous reports showing selective decay of pathogenic nonstop mRNAs, quantitative real‐time PCR and 3'‐RACE‐RFLP analysis revealed unreduced nonstop mRNA levels in our patient and 2 heterozygous carriers of the mutation. The absence of thymidine phosphorylase protein in the homozygous patient, together with the partial decrease in levels of this protein in 2 carriers suggest that the main control system in this case resides at the translational or post‐translational levels rather than through NSD. This is the first report showing an absence of NSD in a human disease, revealing that this surveillance mechanism has exceptions in vivo. © 2011 Wiley‐Liss, Inc.