DNA sequence analysis of the gene encoding subunit 6 of the 
NADH-ubiquinone-oxidoreductase complex (ND6) in human mitochondria was performed 
in 25 independent patients who suffer from Lebers hereditary optic neuropathy 
(LHON). In 10 cases the well-known LHON mutation at nucleotide position (np) 
14484 was detected. Furthermore, silent substitutions at np14167 and np14527 and 
missense mutations at np14498, np14564, np14568, and np14582 were found in 
individual patients. The np14498 and np14568 mutations were found in patients 
who present a typical clinical picture and course of LHON but lack any of the 
canonical mtDNA mutations. The np14568 mutation, which replaces a moderately 
conserved glycine by a serine residue, was observed in a single male patient and 
subsequently excluded in 175 independent controls. The mutation at np14498, 
which replaces an evolutionarily highly conserved tyrosine with a cysteine, was 
found in a multigeneration family with four affected members, the eldest 
carrying a heteroplasmic mixture of mutated and wildtype mtDNA molecules. None 
of 170 analyzed control subjects carried this mutation. These findings provide 
evidence that several allelic ND6 gene mutations may be involved in Lebers 
hereditary optic neuropathy.