Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome.

Abstract

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with mitochondrial DNA (mtDNA) mutations. We describe the distribution of seven different mtDNA mutations and the clinical findings in 334 LHON patients belonging to 29 families. Mutations described only in LHON at nucleotide positions 11778, 3460, and 14484 were found in 15, two, and nine families respectively. In three families none of these mutations was found. Mutations described in LHON but also in controls at nucleotide positions 15257, 13708, 4917, and 4216 were found in one, 10, three and 12 families respectively. Combinations of mtDNA mutations were found in most families. The patient population mainly consisted of 79-2% to 89'5% males except for one family with only 10 of 17 patients being males (58-9%, p-0 036). In 11 families only the 11778 mutation was found; in this group (WX) the affected males had a mean age of onset of 29-2 years and a mean visual outcome of 0-113. In seven families the 14484, 13708, and 4216 mutations were found; in this group (MA) the affected males had a mean age of onset of 22-0 years and a mean visual outcome of 0-442. In two families no mutation was found at all; in this group (YX) the affected males had a mean age of onset of 18-9 years and a mean visual outcome of 0 167. The mean age of onset in the WX group is significantly higher than in the MA group (p< 0-01) and in the YX group (p001).

The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees

“…Several secondary LHON mutations have been found (Wallace and Lott 2003); however, in most cases, their pathogenicity is still uncertain and several studies have yielded conflicting evidence regarding the roles of secondary mutations (Brown et al 2002;Howell 1997;Howell et al 1995;Lodi et al 2000;Oostra et al 1994). Two secondary LHON mutations (G3316A and C3497T) were found, one each in two pedigrees.…”

Hereditary optic neuropathies

“…Although some investigators have claimed that multiple LHONassociated mtDNA mutations may be necessary for visual loss, this has not been corroborated in several studies. 9,11,77 Indeed, case reports of unaffected individuals who even harbour two primary mutations 78,79 make this claim improbable. Similarly, although the underlying mtDNA haplotype may influence the presence, penetrance, or expression of an mtDNA point mutation, 80 this is unlikely to be the major factor in phenotypic expression.…”

Molecular genetic basis of primary inherited optic neuropathies

“…The T14484C mutation is associated with the best visual outcome (6/24 or better in 71% of patients). 12,24,25 In all, 50% of reported patients with the T14484C mutation have some recovery of vision. A younger age of onset of visual loss with this mutation and other mutations is also associated with a better visual outcome, especially if the onset is before the age of 20 years.…”