Home
User Guide
What's in a MalaCard Search Guide Our Sources
Analysis Tools
GeneCards GeneAnalytics GeneAlaCart PathCards VarElect TGex
News and Views Disease Lists/Categories
About
About MalaCards Our Publications Weizmann Institute LifeMap Discovery® Terms of Use MalaCards Team
LHON
MCID: LBR030
MIFTS: 61

Leber Optic Atrophy (LHON)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
Sources

Aliases & Classifications for Leber Optic Atrophy

About this section

MalaCards integrated aliases for Leber Optic Atrophy:

Name: Leber Optic Atrophy 57 75 53 25 59 74 38
Leber Hereditary Optic Neuropathy 12 24 53 25 59 74 15
Leber's Optic Atrophy 12 24 25 29 6
Lhon 24 53 25 59 74
Leber Optic Atrophy, Susceptibility to 57 29 13
Leber's Hereditary Optic Neuropathy 12 25
Optic Atrophy, Hereditary, Leber 44 72
Leber Hereditary Optic Atrophy 25 37
Leber's Optic Neuropathy 24 25
Leber Plus Disease 59 6
Leber's Disease 24 53
Leber Hereditary Optic Neuropathy, Modifier of 57
Lebers Hereditary Optic Neuropathy 55
Hereditary Optic Neuroretinopathy 25
Optic Atrophy, Leber Type 53
Optic Atrophy Leber Type 74
Atrophy, Optic, Leber's 40
Lhon, Modifier of 57
Lhon Plus Disease 59
Loas 57
Loa 74

Characteristics:

Orphanet epidemiological data:

59
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:

57
Inheritance:
x-linked


HPO:

32
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:

MalaCards categories:
Global: Rare diseases Metabolic diseases Genetic diseases
Anatomical: Eye diseases Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 34
Orphanet: 59  
Rare eye diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:705
OMIM 57 308905
KEGG 37 H00068
MeSH 44 D029242
NCIt 50 C84808
SNOMED-CT 68 58610003
ICD10 33 H47.22
ICD10 via Orphanet 34 H47.2
UMLS via Orphanet 73 C0917796
UMLS 72 C0917796
Sources

Summaries for Leber Optic Atrophy

About this section
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 iv deficiency, 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 Analgesics have been mentioned in the context of this disorder. Affiliated tissues include eye, brain and testes, and related phenotypes are slow decrease in visual acuity and mitochondrial respiratory chain defects

NIH Rare Diseases : 53 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 : 37
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 : 74 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 : 75 Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to... more...

More information from OMIM: 308905
GeneReviews: NBK1174
Sources

Related Diseases for Leber Optic Atrophy

About this section

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

(show top 50) (show all 316)
# Related Disease Score Top Affiliating Genes
1 leber optic atrophy and dystonia 34.9 MT-ND6 MT-ND4 MT-ND3 MT-ND1
2 mitochondrial complex iv deficiency 33.0 MT-ND4 MT-CO3 MT-CO2 MT-CO1
3 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 32.0 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3 MT-ND1
4 mitochondrial disorders 31.7 OPA1 MT-ATP6
5 3-methylglutaconic aciduria, type iii 31.4 OPA1 MT-ND6 MT-ND4
6 acute retrobulbar neuritis 31.1 MT-ND4 MT-CYB
7 exposure keratitis 31.0 NDUFA1 MT-ND4
8 ataxia and polyneuropathy, adult-onset 30.9 MT-ND4L MT-ND4 MT-ND3 MT-CO3 MT-ATP8 MT-ATP6
9 scotoma 30.7 OPA1 MT-ND4
10 kearns-sayre syndrome 30.6 MT-ND6 MT-ND5 MT-ND4 MT-ND2 MT-ND1 MT-CYB
11 neuropathy 30.6 MT-ND6 MT-ND5 MT-ND4 MT-ND1 MT-ATP6
12 lactic acidosis 30.6 MT-ND6 MT-ND5 MT-ND4 MT-ND1 MT-CYB MT-CO3
13 dystonia 30.6 MT-ND6 MT-ND4 MT-ND3 MT-ND1 MT-CYB
14 mitochondrial metabolism disease 30.3 OPA1 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5
15 deafness, nonsyndromic sensorineural, mitochondrial 30.3 MT-ND5 MT-ND4 MT-ND2 MT-ND1 MT-CO3 MT-CO2
16 mitochondrial myopathy 30.2 MT-ND6 MT-ND5 MT-ND4 MT-ND2 MT-ND1 MT-CYB
17 optic nerve disease 30.2 OPA1 NDUFA1 MYOC MT-ND6 MT-ND5 MT-ND4L
18 retinitis pigmentosa 30.2 MT-ND5 MT-ND4L MT-ND4 MT-ND3 MT-CYB MT-CO3
19 mitochondrial encephalomyopathy 29.4 NDUFA1 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3
20 leigh syndrome 29.4 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
21 loiasis 12.6
22 mitochondrial complex i deficiency, nuclear type 1 11.8
23 optic atrophy 1 11.8
24 mitochondrial complex i deficiency, mitochondrial type 1 11.8
25 mitochondrial complex iii deficiency, nuclear type 1 11.4
26 mitochondrial complex i deficiency, nuclear type 12 11.4
27 mitochondrial complex i deficiency, nuclear type 30 11.4
28 mitochondrial complex v deficiency, nuclear type 1 11.4
29 mitochondrial complex i deficiency, nuclear type 2 11.4
30 mitochondrial complex i deficiency, nuclear type 4 11.4
31 mitochondrial complex i deficiency, nuclear type 6 11.4
32 mitochondrial complex i deficiency, nuclear type 7 11.4
33 mitochondrial complex i deficiency, nuclear type 8 11.4
34 mitochondrial complex i deficiency, nuclear type 9 11.4
35 mitochondrial complex i deficiency, nuclear type 10 11.4
36 mitochondrial complex i deficiency, nuclear type 11 11.4
37 mitochondrial complex i deficiency, nuclear type 13 11.4
38 mitochondrial complex i deficiency, nuclear type 14 11.4
39 mitochondrial complex i deficiency, nuclear type 15 11.4
40 mitochondrial complex i deficiency, nuclear type 16 11.4
41 mitochondrial complex i deficiency, nuclear type 17 11.4
42 mitochondrial complex i deficiency, nuclear type 18 11.4
43 mitochondrial complex i deficiency, nuclear type 19 11.4
44 mitochondrial complex i deficiency, nuclear type 21 11.4
45 mitochondrial complex i deficiency, nuclear type 22 11.4
46 mitochondrial complex i deficiency, nuclear type 23 11.4
47 mitochondrial complex i deficiency, nuclear type 24 11.4
48 mitochondrial complex i deficiency, nuclear type 25 11.4
49 mitochondrial complex i deficiency, nuclear type 26 11.4
50 mitochondrial complex i deficiency, nuclear type 27 11.4

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



Diseases related to Leber Optic Atrophy
Sources

Symptoms & Phenotypes for Leber Optic Atrophy

About this section

Human phenotypes related to Leber Optic Atrophy:

59 32 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 slow decrease in visual acuity 59 32 hallmark (90%) Very frequent (99-80%) HP:0007924
2 mitochondrial respiratory chain defects 59 32 hallmark (90%) Very frequent (99-80%) HP:0200125
3 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
4 central scotoma 59 32 frequent (33%) Frequent (79-30%) HP:0000603
5 retinal telangiectasia 59 32 frequent (33%) Frequent (79-30%) HP:0007763
6 blurred vision 59 32 frequent (33%) Frequent (79-30%) HP:0000622
7 centrocecal scotoma 59 32 frequent (33%) Frequent (79-30%) HP:0000576
8 retinal vascular tortuosity 59 32 frequent (33%) Frequent (79-30%) HP:0012841
9 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
10 myopathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003198
11 peripheral neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0009830
12 postural tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002174
13 ventricular preexcitation 59 32 occasional (7.5%) Occasional (29-5%) HP:0004309
14 arrhythmia 59 Occasional (29-5%)
15 leber optic atrophy 32 HP:0001112

Symptoms via clinical synopsis from OMIM:

57
Eyes:
susceptibility to optic atrophy

Clinical features from OMIM:

308905

UMLS symptoms related to Leber Optic Atrophy:


ataxia, static tremor
Sources

Drugs & Therapeutics for Leber Optic Atrophy

About this section

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

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

Interventional clinical trials:

(show all 36)
# 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 Study With Idebenone in Patients With Chronic Vision Loss Due to Leber's Hereditary Optic Neuropathy (LHON) Withdrawn NCT01495715 Phase 3 Idebenone;Placebo
8 Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy Unknown status NCT02176733 Phase 2 cyclosporine
9 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
10 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
11 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
12 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
13 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
14 Near-infrared Light-emitting Diode (NIR-LED) Therapy for Leber's Hereditary Optic Neuropathy (LHON) Terminated NCT01389817 Phase 1, Phase 2
15 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
16 A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176 Completed NCT02544217 Phase 1 KH176;placebo
17 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
18 Open-Trial of EPI-743 for Adults With Tourette Syndrome Completed NCT01719523 Phase 1 EPI-743
19 Matching Genotypes and Serotonergic Medications for Alcoholism Completed NCT01113164 Phase 1 Ondansetron and Sertraline
20 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)
21 Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy Completed NCT01267422 rAAV2-ND4
22 Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON) Completed NCT02796274
23 Leber Hereditary Optic Neuropathy (LHON) Historical Case Record Survey Completed NCT01892943
24 A Single Visit, Observational, Follow-up Study of Patients With Leber's Hereditary Optic Neuropathy Following Participation in SNT-II-003 Trial Completed NCT01421381
25 Oral Vitamin B12 as Potential Treatment of Recurrent Aphthous Stomatitis Completed NCT00288769 daily sublingual tablets Vitamin B12 1000 mcg versus placebo
26 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
27 Observational Registry Study of Leber Hereditary Optic Neuropathy (LHON) Affected Patients Recruiting NCT03295071
28 A Non-interventional Study of Clinical Experience in Patients Prescribed Raxone® for the Treatment of Leber's Hereditary Optic Neuropathy (LHON) Recruiting NCT02771379 Idebenone
29 Bone Marrow Derived Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
30 Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months Recruiting NCT03428178 rAAV2-ND4
31 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
32 New Non-invasive Modalities for Assessing Retinal Structure and Function:Preliminary Investigation Recruiting NCT03475173
33 Photobiomodulation & Ketogenic Diet for Treatment of Mid-periphery Retinal Disorders (Diabetic Retinopathy, Dry AMD, Hard Drusen Formation) for Alzheimer's Disease Prevention Recruiting NCT03859245
34 EAP Single Patient: Safety of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected With G11778A ND4 Leber Hereditary Optic Neuropathy Available NCT03672968
35 Tissue Study for Mitochondrial Disorders Enrolling by invitation NCT01803906
36 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

Inferred drug relations via UMLS 72 / NDF-RT 51 :


Idebenone

Cochrane evidence based reviews: optic atrophy, hereditary, leber

Sources

Genetic Tests for Leber Optic Atrophy

About this section

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
Sources

Anatomical Context for Leber Optic Atrophy

About this section

MalaCards organs/tissues related to Leber Optic Atrophy:

41
Eye, Brain, Testes, Bone, Spinal Cord, Retina, Skeletal Muscle
Sources

Publications for Leber Optic Atrophy

About this section

Articles related to Leber Optic Atrophy:

(show top 50) (show all 636)
# Title Authors PMID Year
1
Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation? 38 4 8 71
11169561 2001
2
Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. 9 38 4 71
8644732 1996
3
Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. 38 4 71
18771762 2008
4
A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia. 38 4 71
17562939 2007
5
Leber's hereditary optic neuropathy with dystonia in a Japanese family. 9 4 71
16380132 2006
6
Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. 38 4 71
14735585 2004
7
Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. 38 4 71
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. 38 4 71
8016139 1994
9
An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. 38 4 71
1417830 1992
10
Molecular genetic analysis of a sporadic case of Leber hereditary optic neuropathy. 38 4 71
1734726 1992
11
Heteroplasmy in Leber's hereditary optic neuropathy. 4 71
8240102 1993
12
Cytochrome c oxidase mutations in Leber hereditary optic neuropathy. 9 38 71
8240356 1993
13
Intrafamilial variation in Leber hereditary optic neuropathy revealed by direct mutation analysis. 9 38 71
8448903 1993
14
Cytochrome b mutations in Leber hereditary optic neuropathy. 9 38 71
1764087 1991
15
Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. 9 38 71
1928099 1991
16
The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. 4 71
2039048 1991
17
Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. 4 71
3201231 1988
18
Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. 38 71
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. 38 71
19026397 2008
20
Primary spinal cord neurodegeneration in Leber hereditary optic neuropathy. 38 71
17620555 2007
21
Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. 38 71
16532388 2006
22
The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees. 38 71
16477364 2006
23
Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. 38 8
16380918 2005
24
A "Fille du Roy" introduced the T14484C Leber hereditary optic neuropathy mutation in French Canadians. 38 71
15954041 2005
25
The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy. 9 71
15505787 2004
26
SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. 9 38 4
15293270 2004
27
Sequence analysis of the mitochondrial genomes from Dutch pedigrees with Leber hereditary optic neuropathy. 38 71
12736867 2003
28
From genotype to phenotype in Leber hereditary optic neuropathy: still more questions than answers. 38 8
12464728 2002
29
Rescue of a mitochondrial deficiency causing Leber Hereditary Optic Neuropathy. 38 71
12402249 2002
30
A case-control study of tobacco and alcohol consumption in Leber hereditary optic neuropathy. 38 8
11124301 2000
31
Leber Hereditary Optic Neuropathy 38 71
20301353 2000
32
Mitochondrial Disorders Overview 38 71
20301403 2000
33
Predominance of the T14484C mutation in French-Canadian families with Leber hereditary optic neuropathy is due to a founder effect. 38 71
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. 38 71
9150158 1997
35
Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. 38 71
9012411 1997
36
Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy. 38 8
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. 38 71
7573056 1995
38
When does bilateral optic atrophy become Leber hereditary optic neuropathy? 38 71
8213825 1993
39
The two locus control of Leber hereditary optic neuropathy and a high penetrance in Japanese pedigrees. 38 8
8500789 1993
40
Homoplasmic and exclusive ND4 gene mutation in Japanese pedigrees with Leber's disease. 9 71
8449667 1993
41
A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. 38 71
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. 38 8
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. 38 8
1395084 1992
44
Mitochondrial ND-I mutation in Leber hereditary optic neuropathy. 38 71
1550131 1992
45
Mitochondrial DNA mutation and heteroplasmy in type I Leber hereditary optic neuropathy. 38 71
1346348 1992
46
Mitochondrial DNA mutation in an Italian family with Leber hereditary optic neuropathy. 38 71
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. 38 8
1896469 1991
48
Preliminary exclusion of an X-linked gene in Leber optic atrophy by linkage analysis. 38 8
2731932 1989
49
Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial. 38 4
24525545 2014
50
Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. 38 4
24198293 2013
Sources

Variations for Leber Optic Atrophy

About this section

ClinVar genetic disease variations for Leber Optic Atrophy:

6 (show top 50) (show all 51)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 NDUFS2 NM_004550.4(NDUFS2): c.268G> A (p.Ala90Thr) single nucleotide variant Pathogenic rs1553249704 1:161176262-161176262 1:161206472-161206472
2 MT-ATP6 m.9101T> C single nucleotide variant Pathogenic rs199476134 MT:9101-9101 MT:9101-9101
3 MT-CO3 m.9438G> A single nucleotide variant Pathogenic rs267606611 MT:9438-9438 MT:9438-9438
4 MT-CO1 ; MT-TS1 NC_012920.1: m.7444G> A single nucleotide variant Pathogenic rs199474822 MT:7444-7444 MT:7444-7444
5 MT-CYB m.15812G> A single nucleotide variant Pathogenic rs200336777 MT:15812-15812 MT:15812-15812
6 MT-ND6 NC_012920.1: m.14484T> C single nucleotide variant Pathogenic rs199476104 MT:14484-14484 MT:14484-14484
7 MT-ND6 m.14459G> A single nucleotide variant Pathogenic rs199476105 MT:14459-14459 MT:14459-14459
8 MT-ND6 m.14596A> T single nucleotide variant Pathogenic rs387906424 MT:14596-14596 MT:14596-14596
9 MT-ND6 m.14495A> G single nucleotide variant Pathogenic rs199476106 MT:14495-14495 MT:14495-14495
10 MT-ND6 m.14482C> A single nucleotide variant Pathogenic rs199476108 MT:14482-14482 MT:14482-14482
11 MT-ND5 m.13730G> A single nucleotide variant Pathogenic rs387906425 MT:13730-13730 MT:13730-13730
12 MT-ND5 m.13045A> C single nucleotide variant Pathogenic rs267606895 MT:13045-13045 MT:13045-13045
13 MT-ND5 m.12848C> T single nucleotide variant Pathogenic rs267606899 MT:12848-12848 MT:12848-12848
14 MT-ND4L m.10663T> C single nucleotide variant Pathogenic rs1556423844 MT:10663-10663 MT:10663-10663
15 MT-ND4 NC_012920.1: m.11778G> A single nucleotide variant Pathogenic rs199476112 MT:11778-11778 MT:11778-11778
16 MT-ND4 m.11696G> A single nucleotide variant Pathogenic rs200873900 MT:11696-11696 MT:11696-11696
17 MT-ND2 m.5244G> A single nucleotide variant Pathogenic rs199476115 MT:5244-5244 MT:5244-5244
18 MT-ND2 m.4640C> A single nucleotide variant Pathogenic rs387906426 MT:4640-4640 MT:4640-4640
19 MT-ND1 NC_012920.1: m.3460G> A single nucleotide variant Pathogenic rs199476118 MT:3460-3460 MT:3460-3460
20 MT-ND1 m.4160T> C single nucleotide variant Pathogenic rs199476119 MT:4160-4160 MT:4160-4160
21 MT-ND1 m.3394T> C single nucleotide variant Pathogenic rs41460449 MT:3394-3394 MT:3394-3394
22 MT-ND1 m.4136A> G single nucleotide variant Pathogenic rs199476121 MT:4136-4136 MT:4136-4136
23 MT-ND1 m.4171C> A single nucleotide variant Pathogenic rs28616230 MT:4171-4171 MT:4171-4171
24 MT-ND1 m.3697G> A single nucleotide variant Pathogenic rs199476122 MT:3697-3697 MT:3697-3697
25 MT-ND1 m.3733G> A single nucleotide variant Pathogenic rs199476125 MT:3733-3733 MT:3733-3733
26 MT-ND5 m.12338T> C single nucleotide variant Pathogenic rs201863060 MT:12338-12338 MT:12338-12338
27 MT-ND3 m.10237T> C single nucleotide variant Pathogenic rs1556423787 MT:10237-10237 MT:10237-10237
28 MT-ND4 m.11253T> C single nucleotide variant Pathogenic rs200145866 MT:11253-11253 MT:11253-11253
29 MT-ND5 m.13637A> G single nucleotide variant Pathogenic rs200855215 MT:13637-13637 MT:13637-13637
30 MT-ND6 m.14325T> C single nucleotide variant Pathogenic rs397515505 MT:14325-14325 MT:14325-14325
31 MT-ND6 m.14482C> G single nucleotide variant Pathogenic rs199476108 MT:14482-14482 MT:14482-14482
32 MT-ND6 m.14498T> C single nucleotide variant Pathogenic rs869025186 MT:14498-14498 MT:14498-14498
33 MT-ND6 m.14568C> T single nucleotide variant Pathogenic rs397515506 MT:14568-14568 MT:14568-14568
34 MT-ND6 m.14279G> A single nucleotide variant Pathogenic rs869025187 MT:14279-14279 MT:14279-14279
35 MT-CYB m.14831G> A single nucleotide variant Pathogenic rs199795644 MT:14831-14831 MT:14831-14831
36 MT-ND1 m.3635G> A single nucleotide variant Pathogenic rs397515507 MT:3635-3635 MT:3635-3635
37 MT-ND1 m.3700G> A single nucleotide variant Pathogenic rs397515508 MT:3700-3700 MT:3700-3700
38 MT-ND1 m.4025C> T single nucleotide variant Pathogenic rs397515509 MT:4025-4025 MT:4025-4025
39 MT-ND1 m.3376G> A single nucleotide variant Pathogenic rs397515612 MT:3376-3376 MT:3376-3376
40 NDUFAF5 NM_024120.5(NDUFAF5): c.290G> A (p.Gly97Asp) single nucleotide variant Likely pathogenic rs1555830705 20:13769261-13769261 20:13788615-13788615
41 NDUFAF5 NM_024120.5(NDUFAF5): c.1029dup (p.Ser344fs) duplication Likely pathogenic rs778575439 20:13797847-13797847 20:13817201-13817201
42 MT-CO3 m.9804G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200613617 MT:9804-9804 MT:9804-9804
43 MT-CYB m.15257G> A single nucleotide variant Conflicting interpretations of pathogenicity rs41518645 MT:15257-15257 MT:15257-15257
44 MT-ND5 m.13708G> A single nucleotide variant Conflicting interpretations of pathogenicity rs28359178 MT:13708-13708 MT:13708-13708
45 MT-ND1 m.4216T> C single nucleotide variant Conflicting interpretations of pathogenicity rs1599988 MT:4216-4216 MT:4216-4216
46 MT-ND2 m.4917A> G single nucleotide variant Uncertain significance rs28357980 MT:4917-4917 MT:4917-4917
47 MT-ND5 m.12811T> C single nucleotide variant Uncertain significance rs199974018 MT:12811-12811 MT:12811-12811
48 MT-TL1 NC_012920.1: m.3275C> T single nucleotide variant Uncertain significance rs1057516057 MT:3275-3275 MT:3275-3275
49 MT-ND4 NC_012920.1: m.11360A> G single nucleotide variant Uncertain significance rs878928689 MT:11360-11360 MT:11360-11360
50 MT-CYB NC_012920.1: m.15437G> A single nucleotide variant Uncertain significance rs878853058 MT:15437-15437 MT:15437-15437
Sources

Expression for Leber Optic Atrophy

About this section
Search GEO for disease gene expression data for Leber Optic Atrophy.
Sources

Pathways for Leber Optic Atrophy

About this section

Pathways related to Leber Optic Atrophy according to KEGG:

37
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190

Pathways related to Leber Optic Atrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Metabolism 66
Show member pathways
 13.71 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
2
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. 66
Show member pathways
 12.78 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
3
GABAergic synapse 37
Show member pathways
 12.17 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
4
Cardiac muscle contraction 37
11.49 MT-CYB MT-CO3 MT-CO2 MT-CO1
5
TP53 Regulates Metabolic Genes 66
11.47 MT-CO3 MT-CO2 MT-CO1
6
Metformin Pathway, Pharmacodynamics 61
11.05 NDUFS4 NDUFS2 NDUFA1
Sources

GO Terms for Leber Optic Atrophy

About this section

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 mitochondrial membrane GO:0031966 9.92 OPA1 NDUFA1 MT-ND6 MT-ND4L MT-ND4 MT-ND3
2 mitochondrial respiratory chain complex I GO:0005747 9.81 NDUFS4 NDUFS2 NDUFA1 MT-ND5 MT-ND4L MT-ND4
3 respiratory chain GO:0070469 9.77 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
4 respiratory chain complex IV GO:0045277 9.58 MT-CO3 MT-CO2 MT-CO1
5 mitochondrial inner membrane GO:0005743 9.55 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND6
6 mitochondrial proton-transporting ATP synthase complex GO:0005753 9.52 MT-ATP8 MT-ATP6
7 mitochondrial respiratory chain complex III GO:0005750 9.51 MT-CYB MT-CO1
8 proton-transporting ATP synthase complex, coupling factor F(o) GO:0045263 9.49 MT-ATP8 MT-ATP6
9 NADH dehydrogenase complex GO:0030964 9.48 MT-ND4L MT-ND3
10 mitochondrial respiratory chain complex IV GO:0005751 9.13 MT-CO1
11 integral component of membrane GO:0016021 10.33 OPA1 NDUFA1 MT-ND6 MT-ND5 MT-ND4L MT-ND4
12 membrane GO:0016020 10.32 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND6
13 mitochondrion GO:0005739 10.1 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND5

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

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.97 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
2 response to oxidative stress GO:0006979 9.73 NDUFS2 MT-ND3 MT-CO1
3 aging GO:0007568 9.73 OPA1 MT-ND4 MT-CO1 MT-ATP6
4 proton transmembrane transport GO:1902600 9.71 MT-CO3 MT-CO2 MT-CO1
5 aerobic respiration GO:0009060 9.67 MT-ND4 MT-ND1 MT-CO3 MT-CO1
6 electron transport chain GO:0022900 9.65 NDUFS4 MT-CO2 MT-CO1
7 mitochondrial respiratory chain complex I assembly GO:0032981 9.61 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4
8 cristae formation GO:0042407 9.58 MT-ATP8 MT-ATP6
9 ATP biosynthetic process GO:0006754 9.58 MT-ATP8 MT-ATP6
10 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.58 MT-CO3 MT-CO2 MT-CO1
11 response to electrical stimulus GO:0051602 9.57 OPA1 MT-CO1
12 ATP synthesis coupled electron transport GO:0042773 9.56 MT-ND5 MT-ND4L MT-ND4 MT-CO2
13 ATP synthesis coupled proton transport GO:0015986 9.55 MT-ATP8 MT-ATP6
14 response to copper ion GO:0046688 9.52 MT-CYB MT-CO1
15 respiratory electron transport chain GO:0022904 9.51 MT-CYB MT-CO3
16 electron transport coupled proton transport GO:0015990 9.5 MT-ND4 MT-CYB MT-CO1
17 mitochondrial ATP synthesis coupled proton transport GO:0042776 9.49 MT-ATP8 MT-ATP6
18 response to hyperoxia GO:0055093 9.46 MT-CYB MT-ATP6
19 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.28 NDUFS4 NDUFS2 NDUFA1 MT-ND5 MT-ND4L MT-ND4

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

# Name GO ID Score Top Affiliating Genes
1 electron transfer activity GO:0009055 9.54 NDUFS2 MT-CYB MT-CO3
2 cytochrome-c oxidase activity GO:0004129 9.5 MT-CO3 MT-CO2 MT-CO1
3 NADH dehydrogenase activity GO:0003954 9.46 NDUFS2 MT-ND5 MT-ND4 MT-ND1
4 oxidoreductase activity, acting on NAD(P)H GO:0016651 9.43 NDUFS4 NDUFS2 MT-ND4L
5 oxidoreductase activity GO:0016491 9.43 NDUFS2 MT-ND4L MT-ND2 MT-CYB MT-CO2 MT-CO1
6 proton transmembrane transporter activity GO:0015078 9.4 MT-ATP8 MT-ATP6
7 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.32 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L
Sources

Sources for Leber Optic Atrophy

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Content
Loading form....