Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON)

John Guy, Gerry Shaw, Fred N. Ross-Cisneros, Peter Quiros, Solange R. Salomao, Adriana Berezovsky, Valerio Carelli, William J Feuer, Alfredo A. Sadun

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). Methods: We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. Results: In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml2) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml2) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml2) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). Conclusions: Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.

Original languageEnglish
Pages (from-to)2443-2450
Number of pages8
JournalMolecular Vision
Volume14
StatePublished - Dec 22 2008

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Leber's Hereditary Optic Atrophy
Intermediate Filaments
Pedigree
Age Groups
Nerve Degeneration
Mitochondrial Genome
Optic Nerve
Serum
Sex Characteristics

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Guy, J., Shaw, G., Ross-Cisneros, F. N., Quiros, P., Salomao, S. R., Berezovsky, A., ... Sadun, A. A. (2008). Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON). Molecular Vision, 14, 2443-2450.

Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON). / Guy, John; Shaw, Gerry; Ross-Cisneros, Fred N.; Quiros, Peter; Salomao, Solange R.; Berezovsky, Adriana; Carelli, Valerio; Feuer, William J; Sadun, Alfredo A.

In: Molecular Vision, Vol. 14, 22.12.2008, p. 2443-2450.

Research output: Contribution to journalArticle

Guy, J, Shaw, G, Ross-Cisneros, FN, Quiros, P, Salomao, SR, Berezovsky, A, Carelli, V, Feuer, WJ & Sadun, AA 2008, 'Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON)', Molecular Vision, vol. 14, pp. 2443-2450.
Guy J, Shaw G, Ross-Cisneros FN, Quiros P, Salomao SR, Berezovsky A et al. Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON). Molecular Vision. 2008 Dec 22;14:2443-2450.
Guy, John ; Shaw, Gerry ; Ross-Cisneros, Fred N. ; Quiros, Peter ; Salomao, Solange R. ; Berezovsky, Adriana ; Carelli, Valerio ; Feuer, William J ; Sadun, Alfredo A. / Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON). In: Molecular Vision. 2008 ; Vol. 14. pp. 2443-2450.
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abstract = "Purpose: To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). Methods: We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. Results: In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml2) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml2) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml2) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). Conclusions: Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.",
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AU - Shaw, Gerry

AU - Ross-Cisneros, Fred N.

AU - Quiros, Peter

AU - Salomao, Solange R.

AU - Berezovsky, Adriana

AU - Carelli, Valerio

AU - Feuer, William J

AU - Sadun, Alfredo A.

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N2 - Purpose: To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). Methods: We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. Results: In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml2) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml2) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml2) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). Conclusions: Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.

AB - Purpose: To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). Methods: We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. Results: In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml2) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml2) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml2) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). Conclusions: Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.

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