title: Heteroplasmic mutation in the anticodon-stem of mitochondrial tRNA(Val) causing MNGIE-like gastrointestinal dysmotility and cachexia.
abstract: While mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is typically associated with mutations in the nuclear gene encoding for thymidine phosphorylase (ECGF1, TYMP), a similar clinical phenotype was described in patients carrying mutations in the nuclear-encoded polymerase gamma (POLG1) as well as a few mitochondrial tRNA genes. Here we report a novel mutation in the mitochondrial tRNA(Val) (MTTV) gene in a girl presenting with clinical symptoms of MNGIE-like gastrointestinal dysmotility and cachexia. Clinical, histological, biochemical and single cell investigations were performed. The heteroplasmic m.1630A>G mutation was detected in the mitochondrial tRNA(Val) (MTTV) gene in the patient's muscle, blood leukocytes and myoblasts, as well as in blood DNA of the unaffected mother. We provide clinical, biochemical, histological, and molecular genetic evidence on the single cell level for the pathogenicity of this mutation. Our finding adds to the genetic heterogeneity of MNGIE-like gastrointestinal symptoms and highlights the importance of a thorough genetic workup in case of suspected mitochondrial disease.
authors.affiliation: Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University, Ziemssenstr. 1a, Munich 80336, Germany. Rita.Horvath@ncl.ac.uk
authors.forename: Rita
authors.initials: R
authors.lastname: Horváth
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Birgit
authors.initials: B
authors.lastname: Czermin
authors.forename: Tobias
authors.initials: T
authors.lastname: Trips
authors.forename: Peter
authors.initials: P
authors.lastname: Schneiderat
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000926:Anticodon / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002100:Cachexia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012366:RNA, Transfer, Val / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D000926:Anticodon; D005819:Genetic Markers; D000077278:RNA, Mitochondrial; D012366:RNA, Transfer, Val; D012313:RNA; D014633:Valine