Epidemic Neuropathy in Cuba Not Associated With Mitochondrial DNA Mutations Found in Leber's Hereditary Optic Neuropathy Patients

Newman, Nancy J.; Torroni, Antonio; Brown, Michael D.; Lott, Marie T.; Fernández, Melba Márquez; Wallace, Douglas C.

doi:10.1016/s0002-9394(14)72895-8

Cited by 50 publications

(23 citation statements)

References 34 publications

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“…al., 1991;Mashima et al, 1993;Newman et al, 1994). The current study has confirmed the repeated occurrence of the 11 778 mutation, having shown that it has arisen at least 12 independent times in a sample of 17 11778-positive Caucasian patients (Fig.…”

Section: The 11778 Mutationsupporting

confidence: 79%

“…The 3460 mutation has not been observed in over 630 controls surveyed (Huoponen et al, 1991; Howell et al, 1991a;Johns et al, 1992a;Newman et al, 1994;). Moreover, in the present study, this mutation was shown to have occurred at least nine independent times, one case of which was heteroplasmic (Fig.…”

Section: The 3460 Mutationmentioning

confidence: 99%

“…Moreover, primary mutations are expected to be associated with LHON regardless of mtDNA haplotype. This has been rigorously demonstrated only for the 11778 ND4 mutation (Singh et al, 1989), which is responsible for 50-60% of all Caucasian LHON cases (Newman, 1993), approximately 80% of Japanese LHON cases (Mashima et al, 1993) and has most recently been found in an African mtDNA haplotype in association with LHON (Newman et al, 1994). To-date, the three primary mutations have not been found to co-occur in the same mtDNA.…”

Section: Introductionmentioning

confidence: 99%

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Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations

et al. 1995

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The mitochondrial DNAs (mtDNA) from 17 Caucasian 11778-positive and 30 Caucasian 11778-negative Leber's hereditary optic neuropathy (LHON) patients were PCR-amplified and subjected to high resolution restriction endonuclease analysis. Concurrently, all patient mtDNAs were screened for the common primary LHON mtDNA mutations at nucleotide pairs (nps) 3460, 11778, and 14484, the ambiguous intermediate-risk LHON mtDNA mutations at nps 5244 and 15257, and the secondary LHON mtDNA mutations at nps 3394, 4216, 4917, 7444, 13708, and 15812. Phylogenetic analysis was performed using mtDNA haplotype data from the 47 LHON patients and 175 non-LHON Caucasian controls. The superimposition of the LHON mutation screening results upon the Caucasian mtDNA phylogeny revealed (1) 35 different LHON haplotypes, (2) that all three common primary mutations have occurred multiple times in Caucasians, (3) that while recurrent mutation is common for the primary mutations, secondary mutations tend to be lineage-specific, (4) that the np 15257 mutation was confined to a single mtDNA lineage but may be etiologically important in some LHON cases since it was found in a LHON pedigree which lacked a common primary mutation; complete sequence analysis of the proband mtDNA revealed only a single other candidate missense mutation (at np 10663 of the ND4L gene) of uncertain pathological significance; and (5) that the np 14484 mutation may be less pathogenic than either the np 3460 or np 11778 mutations, as this mutation most commonly occurred on a single mtDNA lineage and almost always in association with secondary LHON mutations. A phylogenetic approach to this genetically heterogeneous disease has thus provided key genetic data bearing on the relative pathogenicity of the LHON-associated mtDNA mutations.

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Section: The 11778 Mutationsupporting

confidence: 79%

Section: The 3460 Mutationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations

et al. 1995

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“…However, widespread nutritional deficiency in Cuba did not appear to increase the expression of LHON in one large 11778-positive pedigree. 82 Similarly, although anecdotal reports suggest a possible role for tobacco and excessive alcohol use as precipitants of visual loss, one lare case-control study of sibships 83 failed to confirm this. Other agents known to be toxic to the optic nerve, such as ethambutol, 84,85 or to mitochondrial function, such as antiretroviral therapy, [86][87][88] may have a heightened toxicity in patients with the LHON mutations and already compromised mitochondrial function.…”

Section: Leber's Hereditary Optic Neuropathymentioning

confidence: 99%

Hereditary optic neuropathies

Newman

Biousse

2004

Eye

153

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Aims To provide a clinical update on the hereditary optic neuropathies. Methods Review of the literature. Results The hereditary optic neuropathies comprise a group of disorders in which the cause of optic nerve dysfunction appears to be hereditable, based on familial expression or genetic analysis. In some hereditary optic neuropathies, optic nerve dysfunction is typically the only manifestation of the disease. In others, various neurologic and systemic abnormalities are regularly observed. Conclusion The most common hereditary optic neuropathies are autosomal dominant optic atrophy (Kjer's disease) and maternally inherited Leber's hereditary optic neuropathy. We review the clinical phenotypes of these and other inherited disorders with optic nerve involvement.

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“…1 During the first 3 years of the epidemic, multiple investigations were carried out in order to determine the cause of this condition. 1,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Several investigations of other toxic and inherited optic neuropathies have determined that this type of optic neuropathy is an acquired mitochondrial disorder mainly because of predominance of papillomacular bundle involvement. 1-4.6,18-20 In 2005, 12 years after the onset of CEON, we began using optical coherence tomography (OCT; Stratus; Allergan, Irvine, California, USA) with the purpose of objectively evaluating the nerve fibre layer to determine residual loss of the retinal nerve fibre layer (RNFL) in affected patients.…”

Section: Introductionmentioning

confidence: 99%

Optical Coherence Tomographic Comparison of Cuban Epidemic and Leber’s Hereditary Optic Neuropathy

Santiesteban-Freixas

Pola-Alvarado

Columbie-Garbey

et al. 2015

Neuro-Ophthalmology

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Following the epidemic of optic and peripheral neuropathy, which occurred in Cuba between 1991 and 1993, a number of patients have been re-evaluated, including testing with optical coherence tomography (OCT) and electrophysiology. At the same time, a number of patients with Leber's hereditary optic neuropathy have also been evaluated. The purpose of this study was to detect residual loss of retinal nerve fibre layer (RNFL) in patients who suffered Cuban epidemic optic neuropathy (CEON), and to compare these findings with those in patients with Leber's hereditary optic neuropathy (LHON). Optical coherence tomography as well as clinical examinations were performed on 11 patients diagnosed with CEON 15 years following the epidemic and 14 patients with LHON. OCT in CEON patients showed thinning of the RNFL in the temporal sector and normal thickness in other quadrants. However, patients with chronic LHON had more diffuse RNFL loss throughout the retina. OCT findings corresponded with clinical findings in CEON and LHON. There was drop out of the papillomacular bundle in both diseases. Two patients in the acute stages of LHON and three LHON carriers showed thinning of the temporal RNFL only. This is the first report of OCT in CEON that shows residual damage in the papillomacular bundle compared with chronic LHON where there is more diffuse and progressive loss of the RNFL. The importance of OCT for the diagnosis and evaluation of similar optic neuropathies is emphasised.

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Epidemic Neuropathy in Cuba Not Associated With Mitochondrial DNA Mutations Found in Leber's Hereditary Optic Neuropathy Patients

Cited by 50 publications

References 34 publications

Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations

Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations

Hereditary optic neuropathies

Optical Coherence Tomographic Comparison of Cuban Epidemic and Leber’s Hereditary Optic Neuropathy

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