Characterization of a novel TYMP splice site mutation associated with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
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.
Taanman
Jan-Willem
JW
Department of Clinical Neurosciences, Institute of Neurology, University College London, Rowland Hill Street, London, United Kingdom. j.taanman@medsch.ucl.ac.uk
Daras
Mariza
M
Albrecht
Juliane
J
Davie
Charles A
CA
Mallam
Elizabeth A
EA
Muddle
John R
JR
Weatherall
Mark
M
Warner
Thomas T
TT
Schapira
Anthony H V
AH
Ginsberg
Lionel
L
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
D004272:DNA, Mitochondrial; D005819:Genetic Markers; D022821:RNA Splice Sites; D003576:Electron Transport Complex IV; D013939:Thymidine Phosphorylase