Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2016 Mar;139(Pt 3):e17.
doi: 10.1093/brain/awv339. Epub 2015 Dec 10.

Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion

Valerio Carelli  1 , Pio d'Adamo  2 , Maria Lucia Valentino  3 , Chiara La Morgia  3 , Fred N Ross-Cisneros  4 , Leonardo Caporali  5 , Alessandra Maresca  3 , Paola Loguercio Polosa  6 , Piero Barboni  7 , Annamaria De Negri  8 , Federico Sadun  9 , Rustum Karanjia  10 , Solange R Salomao  11 , Adriana Berezovsky  11 , Filipe Chicani  11 , Milton Moraes  12 , Milton Moraes Filho  12 , Rubens Belfort Jr  11 , Alfredo A Sadun  13
Affiliations
Comment

Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion

Valerio Carelli et al. Brain. 2016 Mar.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Three brothers with different LHON types. (A) Left panel shows fundus picture and cross-sectional optic nerve histopathology (low and high magnification) of Case 1 (classic LHON, type I), demonstrating optic disc atrophy and profound axonal depletion with residual axons only in the far nasal periphery. Middle panel shows fundus picture and cross-sectional optic nerve histopathology (low and high magnification) of Case 2 (TAA-like LHON, type II), demonstrating sectorial pallor of the temporal sector of the optic disc with selective loss of axons limited to the temporal side of the optic disc, corresponding to the papillo-macular bundle. Right panel shows fundus picture and stratus OCT assessment of retinal nerve fibre layer (RNFL) thickness of Case 3 (TAA-like LHON, type II), demonstrating sectorial pallor of the temporal side of the optic disc, with significant reduction of RNFL limited to the temporal sector, corresponding to the papillo-macular bundle. (B) Humphrey visual field (upper panel) and visual acuity (lower panel) follow up of Case 3, showing a recovery of visual function after he quit smoking at age 61. OD = oculus destrum (right eye); OS = oculus sinistrum (left eye); VA = visual acuity.
Figure 2
Figure 2
Kaplan-Meier curves for age of onset in independent LHON cohorts. (A) Kaplan-Meier curve from Kirkman et al. (2009). Remarkably, the LHON heavy smokers (defined as ‘cumulative smoking’ of pack-years) present with delayed age of onset at ∼40 years or later, whereas the LHON non-smokers and light smokers present the steepest decline across the age of 20. (B) Kaplan-Meier curve in the Italian cohort. The same analysis as in Kirkman et al. (2009) applied to an Italian cohort of LHON patients and unaffected carriers faithfully reproduced the same observation that ‘LHON heavy smokers’ become affected at age 40 or later as opposed to LHON non-smokers and light smokers who become affected across the age of 20.
Figure 3
Figure 3
Distribution of age at onset for non-smokers versus smokers in the Italian LHON cohort. (A) Age at onset versus tobacco smoke. A tight bell-shaped distribution, peaking at about 15 years of age, characterized the age at onset of the LHON non-smokers (pure genetic cases, type I), whereas the group of LHON smokers (type I and type II) had a wider distribution, peaking at about age 28. (B) Age at onset versus tobacco smoke conditioned by gender. Stratifying the previous data by gender, females show a shift to later age at onset in both groups, the LHON non-smokers and smokers. (C) Age at onset versus cumulative tobacco smoke. The age at onset of the LHON non-smokers (pure genetic cases, type I) largely separate from that of LHON smokers (types I and II) at age 30 years. Thus, LHON affected with age at onset <30 are mostly non-smokers mixed with some light-smokers, qualifying the type I patients for which the prevalent disease trigger is the genetic background characterized by still unknown modifying variants.
See this image and copyright information in PMC

Comment in

Comment on

References

    1. Amaral-Fernandes MS, Marcondes AM, Miranda PM, Maciel-Guerra AT, Sartorato EL. Mutations for Leber hereditary optic neuropathy in patients with alcohol and tobacco optic neuropathy. Mol Vis 2011; 17: 3175–9. - PMC - PubMed
    1. Barboni P, Savini G, Valentino ML, La Morgia C, Bellusci C, De Negri AM, et al. Leber's hereditary optic neuropathy with childhood onset. Invest Ophthalmol Vis Sci 2006; 47: 5303–9. - PubMed
    1. Bianco A, Martínez-Romero I, Bisceglia L, D'Agruma L, Favia P, Ruiz-Pesini E, et al. Mitochondrial DNA copy number differentiates the Leber’s hereditary optic neuropathy affected individuals from the unaffected mutation carriers. Brain 2015. Advance Access published on July 24, 2015, doi: 10.1093/brain/awv216. - PubMed
    1. Carelli V, Achilli A, Valentino ML, Rengo C, Semino O, Pala M, et al. Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. Am J Hum Genet 2006; 78: 564–74. - PMC - PubMed
    1. Carelli V, Franceschini F, Venturi S, Barboni P, Savini G, Barbieri G, et al. Grand rounds: could occupational exposure to n-hexane and other solvents precipitate visual failure in leber hereditary optic neuropathy? Environ Health Perspect 2007; 115: 113–15. - PMC - PubMed

MeSH terms