LEBERS HEREDITARY OPTIC NEUROPATHY (LHON)-RELATED MITOCHONDRIAL-DNA SEQUENCE CHANGES IN ITALIAN PATIENTS PRESENTING WITH SPORADIC BILATERALOPTIC NEURITIS

Eighteen Italian patients presenting with sporadic, bilateral, simulta neous, or sequential optic neuritis (ON) were evaluated for 14 base ch anges in mitochondrial DNA (mtDNA) previously found associated with Le ber's hereditary optic neuropathy (LHON), aiming to identify at a mole cular level LHON cases with nontypical phenotypes. During a 36-month f ollow-up, 11 ON patients developed clinical or laboratory features all owing diagnosis of clinically definite multiple sclerosis (MS). None w as positive for any of the ''primary'' LHON-associated mutations. Howe ver, single or multiple ''secondary'' LHON-associated sequence changes at 4216/ND1, 4917/ND2, and 13708/ND5 were detected in ON and ON-MS pa tients. MS controls without visual failure as well as healthy control subjects harbored the same base changes at similar frequencies. In add ition, coexistence of three sequence changes was found in two cases (1 ON-MS patient and 1 MS control patient). We also report finding two n ew neutral sequence base changes in the ND-4 gene which were identifie d by SSCP and confirmed by automated DNA sequence analysis. The result s suggest that these secondary mutations do not contribute to MS susce ptibility in these patients, but rather represent neutral mitochondria l DNA polymorphisms. In addition, whether there are biochemical abnorm alities related to single and multiple secondary mtDNA sequence change s remain to be demonstrated, (C) 1995 Academic Press, Inc.