Leber’s Hereditary Optic Neuropathy Mitochondrial DNA Mutations at Nucleotides 11778 and 3460 in Multiple Sclerosis

Abstract

Objectives: Leber’s hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis seen in multiple sclerosis (MS). About half of the LHON patients harbor a mutation at nucleotide (nt) 11778 in the mitochondrial (mt) DNA. In addition, mutations at nt-3460 and nt-14484 have been associated with LHON. An association of LHON and MS has been suspected for decades, and, recently, the LHON nt-11778 and nt-3460 mtDNA mutations have been found in several patients with MS or MS-like disease. We attempted to determine which MS patients should be evaluated further for LHON mutations. Methods: We screened 103 clinically definite MS patients (age range from 18 to 72 years, 27 men and 76 women) for the LHON nt-11778 and nt-3460 mtDNA mutations. Results: Neither mutation was identified in the patients. Conclusions: Our findings confirm previous reports which found that both LHON mutations are rare in unselected MS patients. The reports to date suggest that MS patients with peripapillary teleangiectasia typical of LHON, with relatives harboring LHON or with early severe bilateral optic neuropathy, particularly if female, should be further evaluated for LHON mutations.

Leber’s Hereditary Optic Neuropathy Mutations in Korean Patients with Multiple Sclerosis

“…Since Harding et al [2]reported on 8 LHON women with the nucleotide (nt) 11778 mutation and multiple sclerosis (MS), many further reports have verified the relationship of LHON and MS [3, 4, 5, 6, 7, 8, 9]. The association of LHON and MS has been reported to be more than a coincidence, and that carrying a primary LHON mutation is a risk factor for developing MS, at least in Caucasian populations [7].…”

Mitochondrial mutations of Leber's hereditary optic neuropathy: a risk factor for multiple sclerosis

“…Several other patients with primary LHON mutations and an MSlike disease have subsequently been reported [1,3,8,9,14,20,23,28,30,32,37,40,42]. A higher frequency of secondary mutations in MS has also been reported [5,17,18], but this finding is questioned since other reports show an equal distribution of the incidence of these secondary mutations in LHON, MS, and the normal population [20,45].…”

Lack of Association between Leber’s Hereditary Optic Neuropathy Primary Point Mutations and Multiple Sclerosis in Iran

“…Vanopdenbosch et al [23]showed that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON mutation is a risk factor for developing MS. Moreover, mitochondrial primary point mutations at np 11,778 or 3,460 have been detected in some individuals affected by MS with an early and severe optic nerve involvement [24, 25]. Meanwhile, the results of several studies suggest a multifactorial etiology for MS, including multiple genetic factors of moderate effect rather than a very few genes of major biologic importance [26].…”