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F. N. Ross-Cisneros, G. Shaw, P. Barboni, C. F. Chicani, A. B. Rosa, K. M. Yee, L. D. Dustin, A. Berezovsky, S. R. Salomao, A. A. Sadun; Asymptomatic Leber's Hereditary Optic Neuropathy Carriers With Subclinical Disease Have Higher Serum Levels of Phosphorylated Neurofilament Heavy Chain. Invest. Ophthalmol. Vis. Sci. 2010;51(13):996.
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Phosphorylated neurofilament heavy chain (pNF-H) is an established serological marker that reflects axonal degeneration. This study investigated the serum assay of pNF-H as a possible quantitative biomarker in asymptomatic carriers belonging to a large Brazilian pedigree with Leber’s Hereditary Optic Neuropathy (LHON).
Human blood samples were collected in Brazil from thirty 11778 LHON haplogroup J carriers (mean age: 36.7) and thirteen controls (off pedigree, mean age: 46.5) with approved IRB's from Brazil and the USA. Blood was clotted and centrifuged at 1,000 rpm for 15 minutes, then samples were kept at -20°C, transferred in dry ice, shipped and stored at -86°C. They were then analysed for pNF-H with an ELISA assay. The level of pNF-H in each asymptomatic carrier was compared to optical coherence tomography (OCT) and Humphrey visual field (HVF) protocols previously published as reliable in identifying sub-clinical changes in LHON.
LHON carriers as a group were not statistically different from controls in their levels of pNF-H. However, the subgroup of LHON carriers with subclinical findings, as demonstrated by OCT, had significantly higher pNF-H levels when compared to increased temporal peripapillary RNFL thickness (p=0.04). There was also a strong trend between high pNF-L levels and RNFL thickness in the inferior quadrant (p=0.07). When the marker was compared to the averaged RNFL thickness of the temporal and inferior quadrants there was also a significant correlation (p=0.04).
Leber's Hereditary Optic Neuropathy is a blinding disease with variable penetrance, but recent studies have identified a subgroup of asymptomatic carriers with subclinical disease. The process of conversion from subclinical disease to affected has been demonstrated with OCT that showed RNFL thickening of the inferior temporal peripapillary RNFL. A serum biomarker, pNF-H strongly correlates with this specific subgroup of carriers and may be a predictor that precedes the blindness that characterizes conversion from carriers to affected in LHON.
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