Familial mitochondrial DNA depletion in liver: haplotype analysis of candidate genes

Hum Genet. 1998 Mar;102(3):327-31. doi: 10.1007/s004390050700.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human / genetics
  • Consanguinity
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Directed DNA Polymerase / genetics
  • Endodeoxyribonucleases / genetics
  • Female
  • Genes / genetics
  • Genetic Linkage
  • Haplotypes*
  • Humans
  • Infant, Newborn
  • Liver Failure / genetics*
  • Male
  • Microsatellite Repeats / genetics
  • Mitochondria, Liver / genetics*
  • Mitochondrial Proteins*
  • NF-E2-Related Factor 1
  • Nuclear Proteins*
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Pedigree
  • Trans-Activators / genetics
  • Transcription Factors / genetics*
  • Trinucleotide Repeats / genetics

Substances

  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • NF-E2-Related Factor 1
  • NRF1 protein, human
  • Nuclear Proteins
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • TFAM protein, human
  • Trans-Activators
  • Transcription Factors
  • mitochondrial transcription factor A
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • Endodeoxyribonucleases
  • endonuclease G