|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Two homoplasmic pathogenic variants (m.9035T>C and m.11778G>A) were identified in 2 out of 928 unrelated individuals (0.2%): the m.9035T>C (MT-ATP6) variant in a female with ataxia and the m.11778G>A (MT-ND4) variant in a male with a complex mosaic disorder and a severe ophthalmological phenotype, uncovering undiagnosed Leber's hereditary optic neuropathy (LHON).
|
31379041 |
2019 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
Biomarker
|
disease |
BEFREE |
To analyse correlations between visual acuity prognosis and baseline characteristics of LHON after rAAV2-ND4 gene therapy.
|
30968497 |
2019 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In this study, we created the patient-specific human induced pluripotent stem cells (hiPSCs) from MT-ND4 mutated LHON-affected patient, asymptomatic mutation carrier and healthy control, and differentiated them into retinal ganglion cells (RGCs).
|
29366807 |
2018 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We here report on the existence of Leber's hereditary optic neuropathy (LHON) associated with peculiar combinations of individually non-pathogenic missense mitochondrial DNA (mtDNA) variants, affecting the MT-ND4, MT-ND4L and MT-ND6 subunit genes of Complex I.
|
29444077 |
2018 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation.
|
26892229 |
2016 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
Biomarker
|
disease |
BEFREE |
Further study in additional patients and in these 9 subjects is needed to better understand the effects of rAAV2-ND4 gene therapy on LHON and to increase the applications of this technique.
|
27426279 |
2016 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
These results suggested that the ND4 gene is the hot spot for mutations associated with LHON.
|
26218905 |
2015 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
These include the severe mutation in the tRNALys gene, m.8363G>A, and the three milder yet prevalent Leber's hereditary optic neuropathy (LHON) mutations in the MT-ND1 (m.3460G>A), MT-ND4 (m.11778G>A) and MT-ND6 (m.14484T>C) mitochondrial genes.
|
25909222 |
2015 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous.
|
24525545 |
2014 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
Biomarker
|
disease |
CTD_human |
Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.
|
24569607 |
2014 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The m.11778G>A mutation in the MT-ND4 gene is associated primarily with LHON; whereas, m.1555A>G in the 12S rRNA gene has been reported with aminoglycoside-induced non-syndromic hearing loss.
|
23805034 |
2013 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes).
|
22879922 |
2012 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Here we report the case of a five year old girl who presented with clinical and neuroradiological findings reminiscent of Leigh syndrome but carried a mtDNA mutation m.11778G>A (p.R340H) in the MTND4 gene usually observed in patients with LHON.
|
21414825 |
2011 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
To create an animal model of Leber Hereditary Optic Neuropathy (LHON), we introduced the human ND4 gene harboring the G11778A mutation, responsible of 60% of LHON cases, to rat eyes by in vivo electroporation.
|
18771762 |
2008 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
G11778A in the subunit ND4 gene of NADH dehydrogenase complex is the most common primary mutation found in Leber's hereditary optic neuropathy (LHON) patients.
|
17320357 |
2007 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Of other variants, the homoplasmic G11696A mutation in the ND4 gene is of special interest as it was implicated to be associated with LHON in a large Dutch family and five Chinese pedigrees with extremely penetrance of visual loss.
|
17300996 |
2007 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Four siblings with a syndrome consisting of encephalomyopathy with hearing impairment, optic nerve atrophy, and cardiac involvement had the 11778G>A mutation in MTND4, previously associated with Leber hereditary optic neuropathy.
|
16044424 |
2005 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
Biomarker
|
disease |
CTD_human |
Leber hereditary optic neuropathy mtDNA mutations disrupt glutamate transport in cybrid cell lines.
|
15342361 |
2004 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Late-onset encephalopathy associated with a C11777A mutation of mitochondrial DNA.
|
12707444 |
2003 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
A novel mtDNA C11777A mutation in Leigh syndrome.
|
16120329 |
2003 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Leber's hereditary optic neuropathy: clinical and molecular genetic results in a patient with a point mutation at np T11253C (isoleucine to threonine) in the ND4 gene and spontaneous recovery.
|
12271374 |
2002 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We employed a microphotometric approach to examine whether a defect in the mitochondrial respiratory complex I expected in Leber hereditary optic neuropathy (LHON) as the consequence of a mtDNA (11778G>A) mutation in the ND4 gene coding for a subunit of the respiratory complex I can be detected at the single-cell level.
|
11117434 |
2000 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
UNIPROT |
Leber's hereditary optic neuropathy in Indonesia: two families with the mtDNA 11778G>A and 14484T>C mutations.
|
9452107 |
1998 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Mutation at position 11778 in the nd4 gene of the human mitochondrial complex I is associated with Leber's hereditary optic neuropathy.
|
9685604 |
1998 |
|
Optic Atrophy, Hereditary, Leber
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
However, RRF and lactic acidosis are absent in Leber hereditary optic neuropathy (LHON) (one point mutation affecting ND4 gene, two point mutations affecting ND1 gene, and one point mutation affecting the apocytochrome b subunit of complex III), and the condition associated with maternally inherited sensory neuropathy (N), ataxia (A), retinitis pigmentosa (RP), developmental delay, dementia, seizures, and limb weakness (NARP) (point mutation affecting ATPase subunit 6 gene).
|
8338207 |
1993 |