title: Characterization of a novel TYMP splice site mutation associated with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
abstract: Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder caused by loss-of-function mutations in the thymidine phosphorylase gene (TYMP). We report here a patient compound heterozygous for two TYMP mutations: a novel g.4009G>A transition affecting the consensus splice donor site of intron 9, and a previously reported g.675G>C splice site mutation. The novel mutation causes exon 9 skipping but leaves the reading frame intact; however, TYMP protein was not detected by immunoblot analysis, suggesting that neither mutant allele is expressed as protein. The patient's fibroblasts showed gradual loss of the mitochondrial DNA-encoded subunit I of cytochrome-c oxidase, suggesting a progressive mitochondrial DNA defect in culture.
authors.affiliation: Department of Clinical Neurosciences, Institute of Neurology, University College London, Rowland Hill Street, London, United Kingdom. j.taanman@medsch.ucl.ac.uk
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Taanman
authors.forename: Mariza
authors.initials: M
authors.lastname: Daras
authors.forename: Juliane
authors.initials: J
authors.lastname: Albrecht
authors.forename: Charles A
authors.initials: CA
authors.lastname: Davie
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mallam
authors.forename: John R
authors.initials: JR
authors.lastname: Muddle
authors.forename: Mark
authors.initials: M
authors.lastname: Weatherall
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: Lionel
authors.initials: L
authors.lastname: Ginsberg
mesh_terms: D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers; D022821:RNA Splice Sites; D003576:Electron Transport Complex IV; D013939:Thymidine Phosphorylase