Leber's hereditary optic neuropathy mitochondrial DNA mutations in familiar multiple sclerosis

Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis due to multiple sclerosis (MS). For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identi fied in several patients with MS-like phenotypes. Tb further study this ass ociation, we tested 42 index patients with clinically definite, familial MS for the LHON mtDNA mutations at nt-3460, nt-1178, and nt-14484. No patient s had a pathogenic LHON mtDNA mutation; however, two MS patients with unila teral optic neuritis harbored the nt-15257 mtDNA polymorphism that was repo rted originally as a pathogenic LHON mutation. Several investigators have s hown evidence that the nt-15257 mtDNA mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, clinically definite MS (95% conf idence intervals for each of the negative mutations 0-7.0%).