title: Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.
abstract: Mitochondrial depletion syndrome (MDS) refers to a heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues. Mutations in DGUOK encoding deoxyguanosine kinase (MIM 601465) cause the hepatocerebral form of MDS (MIM 251880). Cystathioninuria (MIM 219500) can result from mutations in CTH encoding cystathionine gamma lyase (MIM 607657) or can be a secondary finding in several diverse clinical conditions. We present three patients from two apparently unrelated old colony Mennonite families, each of whom had the hepatocerebral form of MDS together with cystathioninuria. Each affected child was homozygous for the novel DGUOK p.D255Y mutation, but had no CTH mutation, indicating that the hepatocerebral form of MDS might be associated with secondary cystathioninuria.
authors.affiliation: Robarts Research Institute and University of Western Ontario, London, Ontario, Canada.
authors.forename: Venu T
authors.initials: VT
authors.lastname: Tadiboyina
authors.forename: Anthony
authors.initials: A
authors.lastname: Rupar
authors.forename: Paul
authors.initials: P
authors.lastname: Atkison
authors.forename: Annette
authors.initials: A
authors.lastname: Feigenbaum
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kronick
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003540:Cystathionine / Q000652:urine*; D003542:Cystathionine gamma-Lyase / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D035781:Siblings; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D003540:Cystathionine; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D003542:Cystathionine gamma-Lyase