LHON
MCID: LBR030
MIFTS: 61

Leber Optic Atrophy (LHON)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leber Optic Atrophy

MalaCards integrated aliases for Leber Optic Atrophy:

Name: Leber Optic Atrophy 56 74 52 25 58 73 37
Leber Hereditary Optic Neuropathy 12 24 52 25 58 73 15
Leber's Optic Atrophy 12 24 25 29 6
Lhon 24 52 25 58 73
Leber Optic Atrophy, Susceptibility to 56 29 13
Leber's Hereditary Optic Neuropathy 12 25
Optic Atrophy, Hereditary, Leber 43 71
Leber Hereditary Optic Atrophy 25 36
Leber's Optic Neuropathy 24 25
Leber Plus Disease 58 6
Leber's Disease 24 52
Leber Hereditary Optic Neuropathy, Modifier of 56
Lebers Hereditary Optic Neuropathy 54
Hereditary Optic Neuroretinopathy 25
Optic Atrophy, Leber Type 52
Optic Atrophy Leber Type 73
Atrophy, Optic, Leber's 39
Lhon, Modifier of 56
Lhon Plus Disease 58
Loas 56
Loa 73

Characteristics:

Orphanet epidemiological data:

58
leber hereditary optic neuropathy
Inheritance: Mitochondrial inheritance; Prevalence: 1-9/100000 (Worldwide); Age of onset: Adolescent,Adult; Age of death: normal life expectancy;
leber plus disease
Inheritance: Mitochondrial inheritance; Prevalence: <1/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
x-linked


HPO:

31
leber optic atrophy:
Inheritance x-linked inheritance


GeneReviews:

24
Penetrance Lhon-causing mtdna pathogenic variants are characterized by reduced penetrance. an individual can only develop lhon if a pathogenic mtdna lhon-causing variant is present, but approximately 50% of males and 90% of females who harbor a primary lhon-causing mtdna pathogenic variant do not develop blindness. it must be stressed that penetrance can vary markedly in different branches of the same family and between families harboring the same lhon-causing mtdna pathogenic variants, which complicates genetic counseling at the individual level. additional environmental and genetic factors interact with the primary mtdna pathogenic variant and determine whether an individual ultimately develops optic nerve dysfunction and visual failure. the two most important risk factors for visual loss are sex and age (see table 4) [yu-wai-man et al 2009]....

Classifications:

Orphanet: 58  
Rare eye diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:705
OMIM 56 308905
KEGG 36 H00068
MeSH 43 D029242
NCIt 49 C84808
SNOMED-CT 67 58610003
ICD10 32 H47.22
ICD10 via Orphanet 33 H47.2
UMLS via Orphanet 72 C0917796
UMLS 71 C0917796

Summaries for Leber Optic Atrophy

Genetics Home Reference : 25 Leber hereditary optic neuropathy (LHON) is an inherited form of vision loss. Although this condition usually begins in a person's teens or twenties, rare cases may appear in early childhood or later in adulthood. For unknown reasons, males are affected much more often than females. Blurring and clouding of vision are usually the first symptoms of LHON. These vision problems may begin in one eye or simultaneously in both eyes; if vision loss starts in one eye, the other eye is usually affected within several weeks or months. Over time, vision in both eyes worsens with a severe loss of sharpness (visual acuity) and color vision. This condition mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Vision loss results from the death of cells in the nerve that relays visual information from the eyes to the brain (the optic nerve). Although central vision gradually improves in a small percentage of cases, in most cases the vision loss is profound and permanent. Vision loss is typically the only symptom of LHON; however, some families with additional signs and symptoms have been reported. In these individuals, the condition is described as "LHON plus." In addition to vision loss, the features of LHON plus can include movement disorders, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Some affected individuals develop features similar to multiple sclerosis, which is a chronic disorder characterized by muscle weakness, poor coordination, numbness, and a variety of other health problems.

MalaCards based summary : Leber Optic Atrophy, also known as leber hereditary optic neuropathy, is related to leber optic atrophy and dystonia and mitochondrial complex i deficiency, nuclear type 1, and has symptoms including ataxia and static tremor. An important gene associated with Leber Optic Atrophy is MT-ND4 (Mitochondrially Encoded NADH:Ubiquinone Oxidoreductase Core Subunit 4), and among its related pathways/superpathways are Oxidative phosphorylation and Metabolism. The drugs Curcumin and Anti-Inflammatory Agents have been mentioned in the context of this disorder. Affiliated tissues include eye, brain and t cells, and related phenotypes are slow decrease in visual acuity and mitochondrial respiratory chain defects

NIH Rare Diseases : 52 Leber hereditary optic neuropathy (LHON) is a condition characterized by vision loss. Vision loss is typically the only symptom of LHON. Some families with additional signs and symptoms have been reported and are said to have "LHON plus ", a condition which includes vision loss, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects ). Some affected individuals develop features similar to multiple sclerosis . LHON is caused by mutations in the MT-ND1 , MT-ND4 , MT-ND4L , and MT-ND6 genes . LHON has a mitochondrial pattern of inheritance; however, there are many cases in which there are no other cases of LHON in the family. Treatment is supportive and may include visual aids. There is ongoing research for more effective treatment.

KEGG : 36 Leber hereditary optic neuropathy (LHON) is a maternally transmitted inherited genetic disease underlying mutation of mitochondrial DNA (mtDNA). It is primarily an ophthalmological disorder, presenting predominantly in young adult males and characterized by acute or subacute bilateral optic atrophy that results in the loss of central vision. In most of the patients with LHON, visual dysfunction is the only manifestation of the disease. The incidence of LHON in Western Europe is 1/30000-1/50000; at least 1 in 14000 males is affected.

UniProtKB/Swiss-Prot : 73 Leber hereditary optic neuropathy: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.

Wikipedia : 74 Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to... more...

More information from OMIM: 308905
GeneReviews: NBK1174

Related Diseases for Leber Optic Atrophy

Diseases related to Leber Optic Atrophy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 318)
# Related Disease Score Top Affiliating Genes
1 leber optic atrophy and dystonia 35.1 MT-ND6 MT-ND4 MT-ND3 MT-ND1
2 mitochondrial complex i deficiency, nuclear type 1 33.8 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND4L MT-ND4
3 mitochondrial complex iv deficiency 33.1 MT-TL1 MT-CO3 MT-CO1
4 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 33.1 NDUFA1 MT-TS1 MT-TL1 MT-ND6 MT-ND5 MT-ND4L
5 mitochondrial disorders 32.0 OPA1 NDUFS4 NDUFS2 NDUFA1 MT-TL1 MT-ND6
6 kearns-sayre syndrome 31.7 MT-TL1 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3
7 chronic progressive external ophthalmoplegia 31.7 MT-TL1 MT-ND6 MT-ND4 MT-CYB MT-ATP6
8 leigh syndrome 31.7 NDUFS4 NDUFS2 NDUFA1 MT-TS1 MT-TL1 MT-ND6
9 mitochondrial metabolism disease 31.7 OPA1 NDUFS4 NDUFS2 NDUFA1 MT-TL1 MT-ND6
10 wolff-parkinson-white syndrome 31.6 MT-TL1 MT-ND5 MT-ND4
11 3-methylglutaconic aciduria, type iii 31.6 OPA1 MT-TL1 MT-ND6 MT-ND4 MT-ND1 MT-CYB
12 lactic acidosis 31.5 NDUFS4 MT-TS1 MT-TL1 MT-ND6 MT-ND5 MT-ND4
13 sensorineural hearing loss 31.5 OPA1 MT-TS1 MT-TL1 MT-ND6 MT-CYB MT-CO1
14 mitochondrial myopathy 31.5 NDUFA1 MT-TS1 MT-TL1 MT-ND6 MT-ND5 MT-ND4L
15 hereditary optic neuropathy 31.4 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND2 MT-ND1
16 mitochondrial non-syndromic sensorineural deafness 31.4 MT-TS1 MT-ND4 MT-CO1
17 deafness, nonsyndromic sensorineural, mitochondrial 31.4 MT-TS1 MT-ND1 MT-CO1
18 optic nerve disease 31.3 OPA1 NDUFA1 MYOC MT-ND6 MT-ND5 MT-ND4L
19 early myoclonic encephalopathy 31.3 NDUFS4 MT-TL1 MT-ND6 MT-ND5 MT-ND4 MT-ATP6
20 retinitis pigmentosa 31.3 OPA1 MYOC MT-TL1 MT-ND6 MT-ND4 MT-ND1
21 optic neuritis 31.2 MT-ND6 MT-ND4 MT-ND1
22 mitochondrial encephalomyopathy 31.2 OPA1 NDUFS4 NDUFA1 MT-TS1 MT-TL1 MT-ND6
23 toxic optic neuropathy 31.2 MT-ND6 MT-ND4
24 open-angle glaucoma 31.1 OPA1 MYOC MT-ND4
25 peripheral nervous system disease 30.9 OPA1 MT-ND6 MT-ND4 MT-ND1 MT-ATP6
26 neuropathy 30.9 OPA1 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3
27 scotoma 30.9 OPA1 MT-ND6 MT-ND4
28 loiasis 12.6
29 optic atrophy 1 11.8
30 mitochondrial complex i deficiency, mitochondrial type 1 11.8
31 mitochondrial complex iii deficiency, nuclear type 1 11.4
32 mitochondrial complex i deficiency, nuclear type 12 11.4
33 mitochondrial complex i deficiency, nuclear type 30 11.4
34 mitochondrial complex v deficiency, nuclear type 1 11.4
35 mitochondrial complex i deficiency, nuclear type 2 11.4
36 mitochondrial complex i deficiency, nuclear type 4 11.4
37 mitochondrial complex i deficiency, nuclear type 6 11.4
38 mitochondrial complex i deficiency, nuclear type 7 11.4
39 mitochondrial complex i deficiency, nuclear type 8 11.4
40 mitochondrial complex i deficiency, nuclear type 9 11.4
41 mitochondrial complex i deficiency, nuclear type 10 11.4
42 mitochondrial complex i deficiency, nuclear type 11 11.4
43 mitochondrial complex i deficiency, nuclear type 13 11.4
44 mitochondrial complex i deficiency, nuclear type 14 11.4
45 mitochondrial complex i deficiency, nuclear type 15 11.4
46 mitochondrial complex i deficiency, nuclear type 16 11.4
47 mitochondrial complex i deficiency, nuclear type 17 11.4
48 mitochondrial complex i deficiency, nuclear type 18 11.4
49 mitochondrial complex i deficiency, nuclear type 19 11.4
50 mitochondrial complex i deficiency, nuclear type 21 11.4

Graphical network of the top 20 diseases related to Leber Optic Atrophy:



Diseases related to Leber Optic Atrophy

Symptoms & Phenotypes for Leber Optic Atrophy

Human phenotypes related to Leber Optic Atrophy:

58 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 slow decrease in visual acuity 58 31 hallmark (90%) Very frequent (99-80%) HP:0007924
2 mitochondrial respiratory chain defects 58 31 hallmark (90%) Very frequent (99-80%) HP:0200125
3 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
4 central scotoma 58 31 frequent (33%) Frequent (79-30%) HP:0000603
5 retinal telangiectasia 58 31 frequent (33%) Frequent (79-30%) HP:0007763
6 blurred vision 58 31 frequent (33%) Frequent (79-30%) HP:0000622
7 centrocecal scotoma 58 31 frequent (33%) Frequent (79-30%) HP:0000576
8 retinal vascular tortuosity 58 31 frequent (33%) Frequent (79-30%) HP:0012841
9 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
10 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
11 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
12 postural tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002174
13 ventricular preexcitation 58 31 occasional (7.5%) Occasional (29-5%) HP:0004309
14 arrhythmia 58 Occasional (29-5%)
15 leber optic atrophy 31 HP:0001112

Symptoms via clinical synopsis from OMIM:

56
Eyes:
susceptibility to optic atrophy

Clinical features from OMIM:

308905

UMLS symptoms related to Leber Optic Atrophy:


ataxia, static tremor

Drugs & Therapeutics for Leber Optic Atrophy

Drugs for Leber Optic Atrophy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 62)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Curcumin Approved, Experimental, Investigational Phase 3 458-37-7 969516
2 Anti-Inflammatory Agents Phase 3
3 Analgesics, Non-Narcotic Phase 3
4 Anti-Inflammatory Agents, Non-Steroidal Phase 3
5 Antirheumatic Agents Phase 3
6 Analgesics Phase 3
7 Central Nervous System Depressants Phase 3
8 Anesthetics Phase 3
9 Pharmaceutical Solutions Phase 3
10 Anti-Infective Agents, Local Phase 3
11
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
12
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
13 Anti-Infective Agents Phase 2
14 Antifungal Agents Phase 2
15 Cyclosporins Phase 2
16 Immunosuppressive Agents Phase 2
17 Calcineurin Inhibitors Phase 2
18 Immunologic Factors Phase 2
19 Ophthalmic Solutions Phase 2
20
Ethanol Approved Phase 1 64-17-5 702
21
Sertraline Approved Phase 1 79617-96-2 68617
22
Ondansetron Approved Phase 1 99614-02-5 4595
23 Dermatologic Agents Phase 1
24 Neuroprotective Agents Phase 1
25 Antipsychotic Agents Phase 1
26 Anti-Anxiety Agents Phase 1
27 Antiemetics Phase 1
28 Serotonin Uptake Inhibitors Phase 1
29 Tranquilizing Agents Phase 1
30 Gastrointestinal Agents Phase 1
31 Neurotransmitter Agents Phase 1
32 Autonomic Agents Phase 1
33 Serotonin Agents Phase 1
34 Psychotropic Drugs Phase 1
35 Antipruritics Phase 1
36 Antidepressive Agents Phase 1
37 Serotonin Antagonists Phase 1
38
Serotonin Investigational, Nutraceutical Phase 1 50-67-9 5202
39
Triamcinolone Approved, Vet_approved 124-94-7 31307
40
Methylcobalamin Approved, Investigational 13422-55-4
41
Hydroxocobalamin Approved 13422-51-0 11953898 15589840
42
Tocopherol Approved, Investigational 1406-66-2, 54-28-4 14986
43
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
44
Cyanocobalamin Approved, Nutraceutical 68-19-9 44176380
45
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
46
Cobalamin Experimental 13408-78-1 6857388
47 Tocotrienol Investigational 6829-55-6
48 Triamcinolone hexacetonide
49 triamcinolone acetonide
50 Triamcinolone diacetate

Interventional clinical trials:

(show all 37)
# Name Status NCT ID Phase Drugs
1 External Natural History Controlled, Open-Label Intervention Study to Assess the Efficacy and Safety of Long-Term Treatment With Raxone® in Leber's Hereditary Optic Neuropathy (LHON) Active, not recruiting NCT02774005 Phase 4 Idebenone
2 A Randomized, Double-blind, Placebo-controlled Trial of Curcumin in Leber's Hereditary Optic Neuropathy (LHON) Completed NCT00528151 Phase 3 curcumin
3 Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and To 12 Months by LHON Due to the G11778A Mutation in the ND4 Gene Completed NCT02652780 Phase 3
4 Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year Active, not recruiting NCT03293524 Phase 3 Placebo
5 Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy Active, not recruiting NCT03153293 Phase 2, Phase 3 rAAV2-ND4
6 A Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for 6 Months or Less by LHON Due to the G11778A Mutation in the Mitochondrial ND4 Gene Active, not recruiting NCT02652767 Phase 3
7 A Randomized, Double-blinded, Placebo-controlled Trial of Idebenone in the Prevention of Episodic Migraine Not yet recruiting NCT04151472 Phase 3 Placebo;90mg Idebenone;270mg Idebenone
8 Study With Idebenone in Patients With Chronic Vision Loss Due to Leber's Hereditary Optic Neuropathy (LHON) Withdrawn NCT01495715 Phase 3 Idebenone;Placebo
9 Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy Unknown status NCT02176733 Phase 2 cyclosporine
10 A Double-Blind, Randomised, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Patients With Leber's Hereditary Optic Neuropathy Completed NCT00747487 Phase 2 Idebenone;Placebo
11 An Exploratory, Double-blind, Randomized, Placebo-controlled, Single-center, Two-way Cross-over Study With KH176 in Patients With the Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation and Clinical Signs of Mitochondrial Disease Completed NCT02909400 Phase 2 KH176;placebo
12 An Open-Label, Dose-Escalating Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease Completed NCT02023866 Phase 2 Cysteamine Bitartrate
13 An Open Label Dose Escalation Clinical Trial to Evaluate the Safety and the Tolerability of GS010 (rAAV2/2-ND4) in Patients With Leber Hereditary Optic Neuropathy Due to Mutations in the Mitochondrial NADH Dehydrogenase 4 Gene Active, not recruiting NCT02064569 Phase 1, Phase 2
14 A Prospective, Randomized, Double-Masked, Vehicle Controlled, Phase 2 Clinical Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide (MTP-131) Topical Ophthalmic Solution in Subjects With Leber's Hereditary Optic Neuropathy (LHON) Active, not recruiting NCT02693119 Phase 2 elamipretide (MTP-131) 1% topical ophthalmic solution;Vehicle topical ophthalmic solution
15 Near-infrared Light-emitting Diode (NIR-LED) Therapy for Leber's Hereditary Optic Neuropathy (LHON) Terminated NCT01389817 Phase 1, Phase 2
16 A Long-Term Open-Label Extension Study of RP103-MITO-001 to Assess the Safety, Tolerability and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease Terminated NCT02473445 Phase 2 Cysteamine Bitartrate
17 A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176 Completed NCT02544217 Phase 1 KH176;placebo
18 A Phase I Open-Label, Dose Escalation Trial of QPI-1007 Delivered by a Single Intravitreal Injection to Patients With Optic Nerve Atrophy (Stratum I) and Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) (Stratum II) Completed NCT01064505 Phase 1 QPI-1007 at various doses
19 Open-Trial of EPI-743 for Adults With Tourette Syndrome Completed NCT01719523 Phase 1 EPI-743
20 Matching Genotypes and Serotonergic Medications for Alcoholism Completed NCT01113164 Phase 1 Ondansetron and Sertraline
21 An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA Recruiting NCT02161380 Phase 1 injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),;injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med);injection of scAAV2-P1ND4v2 2.4 X10e10vg (High);injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
22 Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy Completed NCT01267422 rAAV2-ND4
23 Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON) Completed NCT02796274
24 Leber Hereditary Optic Neuropathy (LHON) Historical Case Record Survey Completed NCT01892943
25 A Single Visit, Observational, Follow-up Study of Patients With Leber's Hereditary Optic Neuropathy Following Participation in SNT-II-003 Trial Completed NCT01421381
26 Oral Vitamin B12 as Potential Treatment of Recurrent Aphthous Stomatitis Completed NCT00288769 daily sublingual tablets Vitamin B12 1000 mcg versus placebo
27 Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials Recruiting NCT03406104
28 Observational Registry Study of Leber Hereditary Optic Neuropathy (LHON) Affected Patients Recruiting NCT03295071
29 A Non-interventional Study of Clinical Experience in Patients Prescribed Raxone® for the Treatment of Leber's Hereditary Optic Neuropathy (LHON) Recruiting NCT02771379 Idebenone
30 Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months Recruiting NCT03428178 rAAV2-ND4
31 Bone Marrow Derived Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
32 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
33 New Non-invasive Modalities for Assessing Retinal Structure and Function:Preliminary Investigation Recruiting NCT03475173
34 Photobiomodulation & Ketogenic Diet for Treatment of Mid-periphery Retinal Disorders (Diabetic Retinopathy, Dry AMD, Hard Drusen Formation) for Alzheimer's Disease Prevention Recruiting NCT03859245
35 EAP Single Patient: Safety of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected With G11778A ND4 Leber Hereditary Optic Neuropathy Available NCT03672968
36 Tissue Study for Mitochondrial Disorders Enrolling by invitation NCT01803906
37 Emergency Administration of EPI-743 to a Single Patient With Leber's Hereditary Optic Neuropathy [LHON] No longer available NCT02300753 EPI-743

Search NIH Clinical Center for Leber Optic Atrophy

Cochrane evidence based reviews: optic atrophy, hereditary, leber

Genetic Tests for Leber Optic Atrophy

Genetic tests related to Leber Optic Atrophy:

# Genetic test Affiliating Genes
1 Leber's Optic Atrophy 29 IVNS1ABP MT-ATP6 MT-CO3 MT-CYB MT-ND2 MT-ND4 MT-ND4L MT-ND5 MT-ND6
2 Leber Optic Atrophy, Susceptibility to 29

Anatomical Context for Leber Optic Atrophy

MalaCards organs/tissues related to Leber Optic Atrophy:

40
Eye, Brain, T Cells, Testes, Spinal Cord, Thyroid, Bone

Publications for Leber Optic Atrophy

Articles related to Leber Optic Atrophy:

(show top 50) (show all 646)
# Title Authors PMID Year
1
Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation? 61 24 56 6
11169561 2001
2
Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. 54 61 24 6
8644732 1996
3
Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. 61 24 6
18771762 2008
4
A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia. 61 24 6
17562939 2007
5
Leber's hereditary optic neuropathy with dystonia in a Japanese family. 54 24 6
16380132 2006
6
Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. 61 24 6
14735585 2004
7
Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. 61 24 6
8755941 1996
8
A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia. 61 24 6
8016139 1994
9
An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. 61 24 6
1417830 1992
10
Molecular genetic analysis of a sporadic case of Leber hereditary optic neuropathy. 61 24 6
1734726 1992
11
Heteroplasmy in Leber's hereditary optic neuropathy. 24 6
8240102 1993
12
Cytochrome c oxidase mutations in Leber hereditary optic neuropathy. 54 61 6
8240356 1993
13
Intrafamilial variation in Leber hereditary optic neuropathy revealed by direct mutation analysis. 54 61 6
8448903 1993
14
Cytochrome b mutations in Leber hereditary optic neuropathy. 54 61 6
1764087 1991
15
Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. 54 61 6
1928099 1991
16
The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. 24 6
2039048 1991
17
Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. 24 6
3201231 1988
18
Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. 61 6
19458970 2009
19
Mitochondrial DNA haplogroups M7b1'2 and M8a affect clinical expression of leber hereditary optic neuropathy in Chinese families with the m.11778G-->a mutation. 61 6
19026397 2008
20
Primary spinal cord neurodegeneration in Leber hereditary optic neuropathy. 61 6
17620555 2007
21
Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. 61 6
16532388 2006
22
The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees. 61 6
16477364 2006
23
Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. 61 56
16380918 2005
24
A "Fille du Roy" introduced the T14484C Leber hereditary optic neuropathy mutation in French Canadians. 61 6
15954041 2005
25
The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy. 54 6
15505787 2004
26
SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. 54 61 24
15293270 2004
27
Sequence analysis of the mitochondrial genomes from Dutch pedigrees with Leber hereditary optic neuropathy. 61 6
12736867 2003
28
From genotype to phenotype in Leber hereditary optic neuropathy: still more questions than answers. 61 56
12464728 2002
29
Rescue of a mitochondrial deficiency causing Leber Hereditary Optic Neuropathy. 61 6
12402249 2002
30
A case-control study of tobacco and alcohol consumption in Leber hereditary optic neuropathy. 61 56
11124301 2000
31
Leber Hereditary Optic Neuropathy 61 6
20301353 2000
32
Mitochondrial Disorders Overview 61 6
20301403 2000
33
Predominance of the T14484C mutation in French-Canadian families with Leber hereditary optic neuropathy is due to a founder effect. 61 6
10631164 2000
34
Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. 61 6
9150158 1997
35
Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. 61 6
9012411 1997
36
Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy. 61 56
8659512 1996
37
Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: molecular, biochemical, and clinical findings. 61 6
7573056 1995
38
When does bilateral optic atrophy become Leber hereditary optic neuropathy? 61 6
8213825 1993
39
The two locus control of Leber hereditary optic neuropathy and a high penetrance in Japanese pedigrees. 61 56
8500789 1993
40
Homoplasmic and exclusive ND4 gene mutation in Japanese pedigrees with Leber's disease. 54 6
8449667 1993
41
A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. 61 6
1463007 1992
42
Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy. 61 56
1415219 1992
43
Leber hereditary optic neuropathy: estimation of number of embryonic precursor cells and disease threshold in heterozygous affected females at the X-linked locus. 61 56
1395084 1992
44
Mitochondrial ND-I mutation in Leber hereditary optic neuropathy. 61 6
1550131 1992
45
Mitochondrial DNA mutation and heteroplasmy in type I Leber hereditary optic neuropathy. 61 6
1346348 1992
46
Mitochondrial DNA mutation in an Italian family with Leber hereditary optic neuropathy. 61 6
1937476 1991
47
X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation. 61 56
1896469 1991
48
Preliminary exclusion of an X-linked gene in Leber optic atrophy by linkage analysis. 61 56
2731932 1989
49
Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial. 61 24
24525545 2014
50
Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. 61 24
24198293 2013

Variations for Leber Optic Atrophy

ClinVar genetic disease variations for Leber Optic Atrophy:

6 (show top 50) (show all 55) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MT-ND6 NC_012920.1:m.14484T>CSNV Pathogenic 9688 rs199476104 MT:14484-14484 MT:14484-14484
2 MT-ND6 m.14459G>ASNV Pathogenic 9689 rs199476105 MT:14459-14459 MT:14459-14459
3 MT-ND6 m.14596A>TSNV Pathogenic 9690 rs387906424 MT:14596-14596 MT:14596-14596
4 MT-ND6 m.14495A>GSNV Pathogenic 9691 rs199476106 MT:14495-14495 MT:14495-14495
5 MT-ND6 m.14482C>ASNV Pathogenic 9693 rs199476108 MT:14482-14482 MT:14482-14482
6 MT-ND5 m.13730G>ASNV Pathogenic 9697 rs387906425 MT:13730-13730 MT:13730-13730
7 MT-ND5 m.13045A>CSNV Pathogenic 9700 rs267606895 MT:13045-13045 MT:13045-13045
8 MT-ND5 m.13042G>ASNV Pathogenic 9703 rs267606898 MT:13042-13042 MT:13042-13042
9 MT-ND5 m.12848C>TSNV Pathogenic 9704 rs267606899 MT:12848-12848 MT:12848-12848
10 MT-ND4L m.10663T>CSNV Pathogenic 9707 rs1556423844 MT:10663-10663 MT:10663-10663
11 MT-ND4 NC_012920.1:m.11778G>ASNV Pathogenic 9708 rs199476112 MT:11778-11778 MT:11778-11778
12 MT-ND4 m.11777C>ASNV Pathogenic 9711 rs28384199 MT:11777-11777 MT:11777-11777
13 MT-ND2 m.5244G>ASNV Pathogenic 9717 rs199476115 MT:5244-5244 MT:5244-5244
14 MT-ND1 NC_012920.1:m.3460G>ASNV Pathogenic 9722 rs199476118 MT:3460-3460 MT:3460-3460
15 MT-ND1 m.4160T>CSNV Pathogenic 9723 rs199476119 MT:4160-4160 MT:4160-4160
16 MT-ND1 m.3697G>ASNV Pathogenic 9733 rs199476122 MT:3697-3697 MT:3697-3697
17 MT-ND1 m.3733G>ASNV Pathogenic 9736 rs199476125 MT:3733-3733 MT:3733-3733
18 MT-ND6 m.14482C>GSNV Pathogenic 65513 rs199476108 MT:14482-14482 MT:14482-14482
19 MT-ND6 m.14568C>TSNV Pathogenic 65515 rs397515506 MT:14568-14568 MT:14568-14568
20 MT-ND1 m.3700G>ASNV Pathogenic 65519 rs397515508 MT:3700-3700 MT:3700-3700
21 MT-ND1 m.3376G>ASNV Pathogenic 65921 rs397515612 MT:3376-3376 MT:3376-3376
22 NDUFS2 NM_004550.4(NDUFS2):c.268G>A (p.Ala90Thr)SNV Pathogenic 522715 rs1553249704 1:161176262-161176262 1:161206472-161206472
23 NDUFAF5 NM_024120.5(NDUFAF5):c.290G>A (p.Gly97Asp)SNV Likely pathogenic 374217 rs1555830705 20:13769261-13769261 20:13788615-13788615
24 NDUFAF5 NM_024120.5(NDUFAF5):c.1029dup (p.Ser344fs)duplication Likely pathogenic 374218 rs778575439 20:13797841-13797842 20:13817195-13817196
25 MT-ND5 NC_012920.1:m.13051G>ASNV Likely pathogenic 430689 rs1131692063 MT:13051-13051 MT:13051-13051
26 MT-ND1 m.4171C>ASNV Likely pathogenic 9732 rs28616230 MT:4171-4171 MT:4171-4171
27 MT-ND1 m.3635G>ASNV Likely pathogenic 65518 rs397515507 MT:3635-3635 MT:3635-3635
28 MT-ND1 m.3394T>CSNV Conflicting interpretations of pathogenicity 9725 rs41460449 MT:3394-3394 MT:3394-3394
29 MT-ND5 m.12811T>CSNV Conflicting interpretations of pathogenicity 65510 rs199974018 MT:12811-12811 MT:12811-12811
30 MT-CO3 m.9804G>ASNV Conflicting interpretations of pathogenicity 9652 rs200613617 MT:9804-9804 MT:9804-9804
31 MT-ND6 m.14279G>ASNV Uncertain significance 65516 rs869025187 MT:14279-14279 MT:14279-14279
32 MT-ND6 m.14498T>CSNV Uncertain significance 65514 rs869025186 MT:14498-14498 MT:14498-14498
33 MT-CYB NC_012920.1(MT-CYB):m.15437G>ASNV Uncertain significance 235525 rs878853058 MT:15437-15437 MT:15437-15437
34 MT-ND4 NC_012920.1:m.11360A>GSNV Uncertain significance 523304 rs878928689 MT:11360-11360 MT:11360-11360
35 MT-ATP6 NC_012920.1:m.8686T>CSNV Uncertain significance 585120 rs1569484231 MT:8686-8686 MT:8686-8686
36 MT-ND6 NC_012920.1(MT-ND6):m.14502T>CSNV Benign 690281 MT:14502-14502 MT:14502-14502
37 MT-TL1 NC_012920.1:m.3275C>TSNV Benign 370045 rs1057516057 MT:3275-3275 MT:3275-3275
38 MT-ND1 m.4025C>TSNV Benign 65520 rs397515509 MT:4025-4025 MT:4025-4025
39 MT-CYB m.14831G>ASNV Benign 65517 rs199795644 MT:14831-14831 MT:14831-14831
40 MT-ND5 m.13637A>GSNV Benign 65511 rs200855215 MT:13637-13637 MT:13637-13637
41 MT-ND6 m.14325T>CSNV Benign 65512 rs397515505 MT:14325-14325 MT:14325-14325
42 MT-ND1 m.4136A>GSNV Benign 9727 rs199476121 MT:4136-4136 MT:4136-4136
43 MT-ND5 m.12338T>CSNV Benign 29999 rs201863060 MT:12338-12338 MT:12338-12338
44 MT-ND3 m.10237T>CSNV Benign 65508 rs1556423787 MT:10237-10237 MT:10237-10237
45 MT-ND4 m.11253T>CSNV Benign 65509 rs200145866 MT:11253-11253 MT:11253-11253
46 MT-ND1 m.4216T>CSNV Benign 9724 rs1599988 MT:4216-4216 MT:4216-4216
47 MT-ND2 m.4640C>ASNV Benign 9718 rs387906426 MT:4640-4640 MT:4640-4640
48 MT-CO1 , MT-TS1 NC_012920.1:m.7444G>ASNV Benign 9663 rs199474822 MT:7444-7444 MT:7444-7444
49 MT-CYB m.15257G>ASNV Benign 9674 rs41518645 MT:15257-15257 MT:15257-15257
50 MT-CYB m.15812G>ASNV Benign 9675 rs200336777 MT:15812-15812 MT:15812-15812

Expression for Leber Optic Atrophy

Search GEO for disease gene expression data for Leber Optic Atrophy.

Pathways for Leber Optic Atrophy

Pathways related to Leber Optic Atrophy according to KEGG:

36
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190

GO Terms for Leber Optic Atrophy

Cellular components related to Leber Optic Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.27 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND6
2 integral component of membrane GO:0016021 10.25 OPA1 NDUFA1 MT-ND6 MT-ND5 MT-ND4L MT-ND4
3 mitochondrion GO:0005739 10.07 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND5
4 mitochondrial membrane GO:0031966 9.87 OPA1 NDUFA1 MT-ND6 MT-ND4L MT-ND4 MT-ND3
5 mitochondrial respiratory chain complex I GO:0005747 9.81 NDUFS4 NDUFS2 NDUFA1 MT-ND5 MT-ND4L MT-ND4
6 respiratory chain GO:0070469 9.73 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
7 mitochondrial inner membrane GO:0005743 9.5 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND6
8 mitochondrial respiratory chain complex III GO:0005750 9.46 MT-CYB MT-CO1
9 respiratory chain complex IV GO:0045277 9.4 MT-CO3 MT-CO1

Biological processes related to Leber Optic Atrophy according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.93 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
2 aging GO:0007568 9.71 OPA1 MT-ND4 MT-CO1 MT-ATP6
3 response to oxidative stress GO:0006979 9.69 NDUFS2 MT-ND3 MT-CO1
4 aerobic respiration GO:0009060 9.62 MT-ND4 MT-ND1 MT-CO3 MT-CO1
5 mitochondrial respiratory chain complex I assembly GO:0032981 9.61 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4
6 ATP synthesis coupled electron transport GO:0042773 9.54 MT-ND5 MT-ND4L MT-ND4
7 response to electrical stimulus GO:0051602 9.52 OPA1 MT-CO1
8 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.49 MT-CO3 MT-CO1
9 respiratory electron transport chain GO:0022904 9.48 MT-CYB MT-CO3
10 response to copper ion GO:0046688 9.46 MT-CYB MT-CO1
11 response to hyperoxia GO:0055093 9.43 MT-CYB MT-ATP6
12 electron transport coupled proton transport GO:0015990 9.43 MT-ND4 MT-CYB MT-CO1
13 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.32 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L

Molecular functions related to Leber Optic Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.72 NDUFS2 MT-ND4L MT-ND2 MT-CYB MT-CO1
2 electron transfer activity GO:0009055 9.43 NDUFS2 MT-CYB MT-CO3
3 cytochrome-c oxidase activity GO:0004129 9.37 MT-CO3 MT-CO1
4 oxidoreductase activity, acting on NAD(P)H GO:0016651 9.33 NDUFS4 NDUFS2 MT-ND4L
5 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.32 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
6 NADH dehydrogenase activity GO:0003954 9.26 NDUFS2 MT-ND5 MT-ND4 MT-ND1

Sources for Leber Optic Atrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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