MITOCHONDRIAL TRANSFER RNATHR MUTATION IN FATAL INFANTILE RESPIRATORY ENZYME DEFICIENCY

The mitochondrial DNA (mtDNA) of two unrelated infants with lethal respiratory chain defects was studied using denaturing gradient gel analysis. This analysis revealed melting behavior differences suggesting a point mutation(s) in a restriction fragment containing the apocytochrome b and tRNAthr genes. Sequencing revealed that patient 1 had an A to G mutation at nt 15924 which is the last base pair of the anticodon stem adjacent to the anticodon loop of tRNAthr. Patient 2 had an A to G mutation at nt 15923 which is the last base of the anticodon loop. The results suggest that mtDNA mutations affecting the anticodon loop structure of tRNAthr cause mitochondrial disease that is fatal in infancy. © 1991.