FAMILIAL MITOCHONDRIAL-DNA DEPLETION IN LIVER - HAPLOTYPE ANALYSIS OFCANDIDATE GENES

Two sons and one daughter of healthy consanguineous parents presented with fatal hepatic failure in association with severe depletion of mit ochondrial (mt)DNA in liver; a third son is healthy. Other published c ases of mtDNA depletion concern single members of a family, which excl udes the use of haplotype analysis. In the family presented here, the inheritance of the genes for mitochondrial transcription factor A (mtT FA), nuclear respiratory factor 1 (NRF-1), mitochondrial single-strand ed DNA-binding protein (mtSSBP), and endonuclease G (EndoG) was studie d using microsatellite markers linked to these genes, The inheritance of the gene for mtDNA polymerase (pol gamma) was studied using a polym orphic 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 inh eritance. Coding sequence analysis of NRF-1 and mtTFA revealed no nove l mutations in affected individuals.