title: Familial mitochondrial DNA depletion in liver: haplotype analysis of candidate genes.
abstract: Two sons and one daughter of healthy consanguineous parents presented with fatal hepatic failure in association with severe depletion of mitochondrial (mt)DNA in liver; a third son is healthy. Other published cases of mtDNA depletion concern single members of a family, which excludes the use of haplotype analysis. In the family presented here, the inheritance of the genes for mitochondrial transcription factor A (mtTFA), nuclear respiratory factor 1 (NRF-1), mitochondrial single-stranded DNA-binding protein (mtSSBP), and endonuclease G (EndoG) was studied using microsatellite markers linked to these genes. The inheritance of the gene for mtDNA polymerase (pol gamma) was studied using a polymorphic CAG repeat present within the coding region of the gene. EndoG and mtSSBP were excluded, but mtTFA remains a candidate. Pol gamma or NRF-1 involvement would be compatible only with autosomal dominant inheritance. Coding sequence analysis of NRF-1 and mtTFA revealed no novel mutations in affected individuals.
authors.affiliation: Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J N
authors.initials: JN
authors.lastname: Spelbrink
authors.forename: M J
authors.initials: MJ
authors.lastname: Van Galen
authors.forename: R
authors.initials: R
authors.lastname: Zwart
authors.forename: H D
authors.initials: HD
authors.lastname: Bakker
authors.forename: A
authors.initials: A
authors.lastname: Rovio
authors.forename: H T
authors.initials: HT
authors.lastname: Jacobs
authors.forename: C
authors.initials: C
authors.lastname: Van den Bogert
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D003241:Consanguinity; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D017093:Liver Failure / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008930:Mitochondria, Liver / Q000235:genetics*; D024101:Mitochondrial Proteins; D051265:NF-E2-Related Factor 1; D009687:Nuclear Proteins; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D010375:Pedigree; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D051265:NF-E2-Related Factor 1; C495633:NRF1 protein, human; D009687:Nuclear Proteins; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; C499631:TFAM protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D004706:Endodeoxyribonucleases; C052391:endonuclease G