A NOVEL GLY290ASP MITOCHONDRIAL CYTOCHROME-B MUTATION LINKED TO A COMPLEX-III DEFICIENCY IN PROGRESSIVE EXERCISE INTOLERANCE

We have identified a new mitochondrial (imt) cytochrome b mutation in a 29-year-old man with progressive exercise muscle intolerance associa ted with a marked deficiency of complex III activity and a decreased a mount of mitochondrial-encoded cytochrome b. This G to A transition at mtDNA position 15615 leads to the substitution (G290D) of a very high ly conserved amino acid of cytochrome b during evolution. The mutant m tDNA was heteroplasmic (80% mutant) in patient muscle but was undetect able in blood from the patient and his healthy mother and sisters. A m aternally inherited cytochrome b polymorphism was also identified in t his patient. Molecular screening of 150 individuals showed that the G2 90D mutation associated with the described phenotype. We suggest that this molecular defect is the primary cause of the muscle disease in th is patient. (C) 1996 Academic Press Limited