Optic Nerve Head Size Correlates With Penetrance in Maternal Lineages Belonging to the Same Large Brazilian SOA-BR Family With Leber’s Hereditary Optic Neuropathy

Abstract

Purpose:: To correlate the optic nerve head (ONH) size with disease penetrance in single maternal lineages belonging to a very large Brazilian pedigree with Leber’s hereditary optic neuropathy (LHON) carrying the 11778/ND4 mutation on a haplogroup J background. We have previously shown that large disc size is a protective factor, which maintains mutation carriers as unaffected (Savini et al. ARVO 2006 #B674).

Methods:: We considered single maternal lineages (n=12), extending up to four generations and including 106 individuals carrying the 11778/ND4 mutation, all belonging to the same very large SOA-BR LHON family previously described. For each maternal lineage the penetrance was evaluated as number of LHON affected individuals out of the total number of mutation carriers. We then correlated the penetrance with the mean optic disc area and vertical disc diameter, as evaluated by Stratus OCT (fast optic disc acquisition protocol). One randomly selected eye was considered for each patient. Correlation between penetrance and optic disc parameters was evaluated using Spearman’s correlation coefficient.

Results:: Optic disc parameters (area and vertical diameter) were available for 70 individuals carrying the mutation, 24 of which were affected with LHON. The variability of penetrance in the 12 maternal lineages investigated ranged from 0% to 100%. The mean optic disc area ranged from 1.17 mm² to 3.14 mm², whereas the mean vertical disc diameter ranged from 1.67 mm to 2.05 mm. The correlation of both optic disc parameters with penetrance of each maternal lineage was statistically significant (p<0.05, R=0.691 for disc area; p<0.01, R=0.726 for vertical disc diameter).

Conclusions:: Our current data show that different maternal branches with low and high disease penetrance, belonging to the same very large SOA-BR LHON pedigree, present statistically significant correlation of disease penetrance with optic disc size. This observation remarks the previous conclusion that a large optic disc size is a protective factor maintaining mutation carriers in the unaffected status.

Keywords: optic nerve • genetics • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)