THE SPECTRUM OF MITOCHONDRIAL-DNA MUTATIONS IN FAMILIES WITH LEBER HEREDITARY OPTIC NEURORETINOPATHY

The mitochondrial complex I genes were sequenced in seven Leber heredi tary optic neuroretinopathy (LHON) families without the ND4/11778 and ND1/3460 mutations. Four replacement mutations restricted only to LHON families were found, one in the ND1 gene at nt 4025, and three in the ND5 gene at nt 12811, 13 637, and 13 967. The mutations did not chang e evolutionarily conserved amino acids suggesting that they are not pr imary LHON mutations in these families. They may be considered as seco ndary LHON mutations serving as exacerbating factors in an appropriate genetic background. A complex III mutation, cyt b/15 257, has been su ggested to be one of the primary mutations causing LHON. Its presence was determined for 23 Finnish LHON families, and it was detected in tw o families harboring the ND4/11 778 mutation. Similarly, complex IV mu tation COI/7444 was screened in Finnish LHON families, and it was foun d in one family carrying the ND1/3460 mutation.