LHON mutations in Italian patients affected by multiple sclerosis

The occurrence of a multiple sclerosis (MS)-like phenotype in subjects carrying mitochondrial DNA (mtDNA) mutations associated with Leber hereditary optic neuropathy (LHON) has suggested that mitochondrial genes may contribute to susceptibility to MS. With the present study 74 unrelated Italian patients (53 females and 21 males; mean age 37.9, SD 9.9, range 20-59) affected by MS with early and prominent optic nerve involvement and 99 normal control subjects were analysed for the presence of primary (nps 11778, 3460, 14484) and an alleged secondary one (np 15257) LHON mutations. A single MS patient carrying a virtually homoplasmic LHON mutation at np 11778 was found. Family history revealed a maternal uncle affected by MS, decreased at age of 64 in consequence of a stroke. The patient's mother harboured the same mutation in a homoplasmic way. Primary LHON mutations were not detected in any other MS patient or control. Of the MS patients 5.4% (4 out of 74), and 5.1% (5 out of 99) of the controls carried the 15257 mutation in a homoplasmic state. Present data do not support any contribution of primary LHON mutations to genetically determined susceptibility in MS. There is no evidence that the 15257 mutation has any pathogenetic significance in the Italian population.