A novel TYMP mutation in a French Canadian patient with mitochondrial neurogastrointestinal encephalomyopathy.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder characterized by gastrointestinal, extraocular muscle, peripheral nerve, and cerebral white matter involvement. Mutations in the nuclear gene TYMP encoding for thymidine phosphorylase (TP) cause loss of TP activity, systemic accumulation of its substrates in plasma and tissues, as well as alterations in mitochondrial DNA including deletions, depletion, and somatic point mutations. To date, more than 30 mutations have been reported in diverse ethnic populations. We present herein the clinical, neuroimaging, neuromuscular, and molecular findings of the first French Canadian patient with MNGIE caused by a novel homozygous invariant splicing site (IVS5 +1 G>A) mutation of the TYMP gene.
Laforce
Robert
R
Département des Sciences Neurologiques, Centre Hospitalier Affilié Universitaire de Québec, Hôpital de l'Enfant-Jésus, Québec, Canada. robert.laforce-jr.1@ulaval.ca
Valdmanis
Paul N
PN
Dupré
Nicolas
N
Rouleau
Guy A
GA
Turgeon
Alexis F
AF
Savard
Martin
M
D002100:Cachexia / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics*; D017615:Enteric Nervous System / Q000503:physiopathology*; D017809:Fatal Outcome; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics* / Q000503:physiopathology; D005769:Gastrointestinal Motility; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics; D013577:Syndrome; D013939:Thymidine Phosphorylase / Q000235:genetics*; D055815:Young Adult
D016228:Endothelial Growth Factors; D020033:Protein Isoforms; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase