LOAM
MCID: LBR038
MIFTS: 62

Leber Hereditary Optic Neuropathy, Modifier of (LOAM)

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

Aliases & Classifications for Leber Hereditary Optic Neuropathy, Modifier of

MalaCards integrated aliases for Leber Hereditary Optic Neuropathy, Modifier of:

Name: Leber Hereditary Optic Neuropathy, Modifier of 57 37
Leber Hereditary Optic Neuropathy 57 12 25 20 43 58 73 15
Leber Optic Atrophy 57 74 20 43 58 73
Lhon 57 25 20 43 58 73
Leber's Optic Atrophy 12 25 43 29 6
Leber Optic Atrophy, Susceptibility to 57 29 13
Leber's Hereditary Optic Neuropathy 12 43
Leber Hereditary Optic Atrophy 43 36
Leber's Optic Neuropathy 25 43
Leber's Disease 25 20
Leber Hereditary Optic Neuropathy; Lhon 57
Lebers Hereditary Optic Neuropathy 54
Hereditary Optic Neuroretinopathy 43
Optic Atrophy, Hereditary, Leber 44
Leber Optic Atrophy ; Loas 57
Optic Atrophy, Leber Type 20
Optic Atrophy Leber Type 73
Atrophy, Optic, Leber's 39
Lhon, Modifier of 57
Loam 57
Loas 57
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;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
x-linked dominant

Miscellaneous:
onset mainly in the second decade of life


HPO:

31
leber hereditary optic neuropathy, modifier of:
Inheritance x-linked inheritance

leber optic atrophy:
Inheritance heterogeneous mitochondrial inheritance
Onset and clinical course incomplete penetrance


GeneReviews:

25
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® 57 308905 535000
KEGG 36 H00068
MeSH 44 D029242
NCIt 50 C84808
SNOMED-CT 67 194045006
ICD10 32 H47.22
ICD10 via Orphanet 33 H47.2
UMLS via Orphanet 72 C0917796
Orphanet 58 ORPHA104
UMLS 71 C0917796

Summaries for Leber Hereditary Optic Neuropathy, Modifier of

MedlinePlus Genetics : 43 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 Hereditary Optic Neuropathy, Modifier of, 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 Hereditary Optic Neuropathy, Modifier of is MT-ND6 (Mitochondrially Encoded NADH:Ubiquinone Oxidoreductase Core Subunit 6), and among its related pathways/superpathways are Oxidative phosphorylation and Metabolism. The drugs Diethylcarbamazine and Curcumin have been mentioned in the context of this disorder. Affiliated tissues include eye, bone marrow and bone, and related phenotypes are mitochondrial respiratory chain defects and slow decrease in visual acuity

GARD : 20 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.

OMIM® : 57 Leber optic atrophy, also known as Leber hereditary optic atrophy (LHON; 535000), is characterized by bilateral, painless, subacute central vision loss in young adults resulting from primary degeneration of retinal ganglion cells (RGCs) accompanied by ascending optic atrophy (summary by Yu et al., 2020). Variation in mitochondrial DNA (mtDNA) contributes to the pathogenesis of the disease. Modifier of Leber optic atrophy (LOAM) exhibits increased penetrance and earlier age of onset compared to Leber optic atrophy caused by the LHON11778A mutation in the MTND4 gene (516003.0001) alone, due to the action of mutation in PRICKLE3 as a modifier of expression of the disease. For a general description and discussion of genetic heterogeneity of Leber optic atrophy, see 535000. (308905) (Updated 05-Mar-2021)

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...

GeneReviews: NBK1174

Related Diseases for Leber Hereditary Optic Neuropathy, Modifier of

Diseases related to Leber Hereditary Optic Neuropathy, Modifier of via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 342)
# Related Disease Score Top Affiliating Genes
1 leber optic atrophy and dystonia 33.5 MT-ND6 MT-ND4 MT-ND3 MT-ND1
2 mitochondrial complex i deficiency, nuclear type 1 33.3 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND4L MT-ND4
3 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 32.6 NDUFS2 NDUFA1 MT-TS1 MT-ND6 MT-ND5 MT-ND4L
4 hereditary optic neuropathy 32.2 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND2 MT-ND1
5 leber plus disease 32.2 PRICKLE3 NDUFS2 MT-TS1 MT-ND6 MT-ND5 MT-ND4L
6 neuropathy 32.2 OPA1 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5
7 optic nerve disease 32.2 OPA1 NDUFS4 NDUFA1 MYOC MT-ND6 MT-ND5
8 dystonia 31.8 MT-ND6 MT-ND4 MT-ND3 MT-ND1 MT-CYB
9 mitochondrial metabolism disease 31.6 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND4 MT-ND3
10 mitochondrial disorders 31.6 OPA1 NDUFS4 NDUFA1 MT-ND6 MT-ND5 MT-ND4
11 kearns-sayre syndrome 31.6 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3 MT-ND2
12 myopathy 31.5 OPA1 NDUFS4 NDUFA1 MT-TS1 MT-ND6 MT-ND5
13 leigh syndrome 31.5 NDUFS4 NDUFS2 NDUFA1 MT-TS1 MT-ND6 MT-ND5
14 chronic progressive external ophthalmoplegia 31.5 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3 MT-ND1
15 mitochondrial myopathy 31.3 MT-TS1 MT-ND6 MT-ND5 MT-ND4L MT-ND4 MT-ND3
16 mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes 31.3 MT-TS1 MT-ND6 MT-ND5 MT-ND4 MT-ND1 MT-ATP6
17 lactic acidosis 31.3 NDUFS4 MT-TS1 MT-ND6 MT-ND5 MT-ND4 MT-ND1
18 3-methylglutaconic aciduria, type iii 31.3 OPA1 MT-ND6 MT-ND4 MT-ND1 MT-CYB MT-CO1
19 scotoma 31.3 OPA1 MT-ND6 MT-ND4
20 sensorineural hearing loss 31.3 OPA1 MT-TS1 MT-ND6 MT-ND5 MT-CYB MT-CO1
21 peripheral nervous system disease 31.3 OPA1 MT-ND6 MT-ND4 MT-ND1 MT-ATP6
22 early myoclonic encephalopathy 31.1 NDUFS4 MT-ND6 MT-ND5 MT-ND4 MT-ATP6
23 deafness, nonsyndromic sensorineural, mitochondrial 31.1 MT-TS1 MT-ND4 MT-ND1 MT-CO1
24 optic atrophy 4 31.1 OPA1 MT-ND6 MT-ND4
25 mitochondrial encephalomyopathy 31.1 OPA1 NDUFS4 NDUFA1 MT-TS1 MT-ND6 MT-ND5
26 retinitis pigmentosa 31.0 MYOC MT-ND6 MT-ND4 MT-ND1 MT-CYB MT-CO3
27 hypertrophic cardiomyopathy 31.0 OPA1 NDUFS4 MT-ND1 MT-CYB MT-CO3 MT-CO1
28 toxic optic neuropathy 31.0 MT-ND6 MT-ND4
29 exposure keratitis 30.9 NDUFA1 MT-ND4
30 loiasis 11.8
31 leber hereditary optic neuropathy with demyelinating disease of cns 11.6
32 optic atrophy 1 11.4
33 mitochondrial complex iv deficiency, nuclear type 1 11.4
34 mitochondrial complex i deficiency, mitochondrial type 1 11.3
35 mitochondrial complex iii deficiency, nuclear type 1 11.3
36 mitochondrial complex ii deficiency, nuclear type 1 11.3
37 mitochondrial complex i deficiency, nuclear type 12 11.3
38 mitochondrial complex i deficiency, nuclear type 30 11.3
39 mitochondrial complex v deficiency, nuclear type 1 11.3
40 mitochondrial complex i deficiency, nuclear type 6 11.3
41 mitochondrial complex i deficiency, nuclear type 7 11.3
42 mitochondrial complex i deficiency, nuclear type 8 11.3
43 mitochondrial complex i deficiency, nuclear type 9 11.3
44 mitochondrial complex i deficiency, nuclear type 10 11.3
45 mitochondrial complex i deficiency, nuclear type 11 11.3
46 mitochondrial complex i deficiency, nuclear type 13 11.3
47 mitochondrial complex i deficiency, nuclear type 14 11.3
48 mitochondrial complex i deficiency, nuclear type 15 11.3
49 mitochondrial complex i deficiency, nuclear type 16 11.3
50 mitochondrial complex i deficiency, nuclear type 17 11.3

Graphical network of the top 20 diseases related to Leber Hereditary Optic Neuropathy, Modifier of:



Diseases related to Leber Hereditary Optic Neuropathy, Modifier of

Symptoms & Phenotypes for Leber Hereditary Optic Neuropathy, Modifier of

Human phenotypes related to Leber Hereditary Optic Neuropathy, Modifier of:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 mitochondrial respiratory chain defects 58 31 hallmark (90%) Very frequent (99-80%) HP:0200125
2 slow decrease in visual acuity 58 31 hallmark (90%) Very frequent (99-80%) HP:0007924
3 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
4 retinal telangiectasia 58 31 frequent (33%) Frequent (79-30%) HP:0007763
5 blurred vision 58 31 frequent (33%) Frequent (79-30%) HP:0000622
6 central scotoma 58 31 frequent (33%) Frequent (79-30%) HP:0000603
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 optic neuropathy 31 frequent (33%) HP:0001138
10 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
11 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
12 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
13 postural tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002174
14 ventricular preexcitation 58 31 occasional (7.5%) Occasional (29-5%) HP:0004309
15 arrhythmia 58 31 Occasional (29-5%) HP:0011675
16 dystonia 31 HP:0001332
17 polyneuropathy 31 HP:0001271
18 visual loss 31 HP:0000572
19 leber optic atrophy 31 HP:0001112
20 central retinal vessel vascular tortuosity 31 HP:0007768

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Eyes:
optic atrophy
reduced visual acuity, moderate to profound

Clinical features from OMIM®:

308905 535000 (Updated 05-Mar-2021)

UMLS symptoms related to Leber Hereditary Optic Neuropathy, Modifier of:


ataxia, static tremor

Drugs & Therapeutics for Leber Hereditary Optic Neuropathy, Modifier of

Drugs for Leber Hereditary Optic Neuropathy, Modifier of (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 47)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Diethylcarbamazine Approved, Investigational, Vet_approved Phase 4 90-89-1 3052
2
Curcumin Approved, Experimental, Investigational Phase 3 458-37-7 969516
3
Bezafibrate Approved, Investigational Phase 2, Phase 3 41859-67-0 39042
4 Anti-Inflammatory Agents Phase 3
5 Analgesics, Non-Narcotic Phase 3
6 Anti-Inflammatory Agents, Non-Steroidal Phase 3
7 Analgesics Phase 3
8 Antirheumatic Agents Phase 3
9 Anti-Infective Agents, Local Phase 3
10 Lipid Regulating Agents Phase 2, Phase 3
11 Antimetabolites Phase 2, Phase 3
12 Hypolipidemic Agents Phase 2, Phase 3
13 Pharmaceutical Solutions Phase 3
14 Anesthetics Phase 3
15
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
16
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
17
Reslizumab Approved, Investigational Phase 2 241473-69-8
18
Ivermectin Approved, Investigational, Vet_approved Phase 2 70288-86-7 6474909
19 Antifungal Agents Phase 2
20 Immunosuppressive Agents Phase 2
21 Immunologic Factors Phase 2
22 Cyclosporins Phase 2
23 Dermatologic Agents Phase 2
24 Calcineurin Inhibitors Phase 2
25 Ophthalmic Solutions Phase 2
26 Respiratory System Agents Phase 2
27 Anti-Asthmatic Agents Phase 2
28 Immunoglobulins Phase 2
29 Antibodies Phase 2
30 Antibodies, Monoclonal Phase 2
31 Protein Kinase Inhibitors Phase 2
32 Vitamins Phase 2
33 Imatinib Mesylate Phase 2 220127-57-1 123596
34 Anti-Infective Agents Phase 2
35 Antiparasitic Agents Phase 2
36 Anthelmintics Phase 2
37 Milbemycin Phase 2
38
Triamcinolone Approved, Vet_approved 124-94-7 31307
39
Tocopherol Approved, Investigational 1406-66-2
40
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
41 Tocotrienol Investigational 6829-55-6
42 Triamcinolone hexacetonide
43 triamcinolone acetonide
44 Triamcinolone diacetate
45 Tocotrienols
46 Tocotrienol, alpha
47 Tocopherols

Interventional clinical trials:

(show all 32)
# Name Status NCT ID Phase Drugs
1 Comparison Between the Post-Treatment Reactions After Single-dose Ivermectin or DEC in Subjects With Loa Loa Infection Completed NCT01593722 Phase 4 Diethylcarbamazine;Ivermectin
2 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
3 A Randomized, Double-blind, Placebo-controlled Trial of Curcumin in Leber's Hereditary Optic Neuropathy (LHON) Completed NCT00528151 Phase 3 curcumin
4 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
5 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 Completed NCT02652767 Phase 3
6 Study of Efficacy of Befizal® 200 mg for the Treatment of Leber Hereditary Optic Neuropathy Recruiting NCT04561466 Phase 2, Phase 3 Béfizal
7 Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials Active, not recruiting NCT03406104 Phase 3
8 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
9 A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber's Hereditary Optic Neuropathy Active, not recruiting NCT03153293 Phase 2, Phase 3 rAAV2-ND4
10 Study With Idebenone in Patients With Chronic Vision Loss Due to Leber's Hereditary Optic Neuropathy (LHON) Withdrawn NCT01495715 Phase 3 Idebenone;Placebo
11 Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy Unknown status NCT02176733 Phase 2 cyclosporine
12 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) Completed NCT02693119 Phase 2 elamipretide (MTP-131) 1% topical ophthalmic solution;Vehicle topical ophthalmic solution
13 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
14 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 Completed NCT02064569 Phase 1, Phase 2
15 A Randomized, Placebo-controlled, Double-Blind Pilot Study of Single-Dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa Loa Infection Completed NCT01111305 Phase 2 Reslizumab;Diethylcarbamazine
16 A Double-Blinded, Randomized, Placebo-Controlled Dose Escalation Study to Examine the Microfilaricidal Kinetics and Safety of Imatinib for the Treatment of Loa Loa (A Pilot Study) Active, not recruiting NCT02644525 Phase 2 Imatinib Mesylate;Placebo
17 Randomized Clinical Trial, Double-blind, Single-dose Drug and Escalating Infection Intensities, Evaluating the Safety and Efficacy of Moxidectin 2 mg, Ivermectin-controlled, in Loa Loa Microfilaremic Patients Not yet recruiting NCT04049851 Phase 2 Moxidectin 2 MG Oral Tablet;Ivermectin 3Mg Tab;Placebo oral tablet
18 Randomized Clinical Trial, Double-blind, Dose-escalating of Drug Intensities, Evaluating the Safety and Efficacy of Levamisole in Loa Loa Microfilaremic Patients Not yet recruiting NCT04049630 Phase 2 LEV 1 mg/kg;LEV 1,5 mg/kg;Placebo
19 Near-infrared Light-emitting Diode (NIR-LED) Therapy for Leber's Hereditary Optic Neuropathy (LHON) Terminated NCT01389817 Phase 1, Phase 2
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 Active, not 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 A Single Visit, Observational, Follow-up Study of Patients With Leber's Hereditary Optic Neuropathy Following Participation in SNT-II-003 Trial Completed NCT01421381
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 Observational Registry Study of Leber Hereditary Optic Neuropathy (LHON) Affected Patients Completed NCT03295071
25 Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy Completed NCT01267422 rAAV2-ND4
26 New Non-invasive Modalities for Assessing Retinal Structure and Function:Preliminary Investigation Recruiting NCT03475173
27 Bone Marrow Derived Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
28 A Non-interventional Study of Clinical Experience in Patients Prescribed Raxone® for the Treatment of Leber's Hereditary Optic Neuropathy (LHON) Active, not recruiting NCT02771379 Idebenone
29 Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months Active, not recruiting NCT03428178 rAAV2-ND4
30 EAP Single Patient: Safety of Bilateral Intravitreal Injection of GS010 in a Single Subject Affected With G11778A ND4 Leber Hereditary Optic Neuropathy Available NCT03672968
31 Expanded Access Program for Idebenone in Patients With Leber's Hereditary Optic Neuropathy Who Completed the LEROS Study Available NCT04381091 Idebenone 150 MG Oral Tablet
32 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 Hereditary Optic Neuropathy, Modifier of

Cochrane evidence based reviews: optic atrophy, hereditary, leber

Genetic Tests for Leber Hereditary Optic Neuropathy, Modifier of

Genetic tests related to Leber Hereditary Optic Neuropathy, Modifier of:

# 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 PRICKLE3

Anatomical Context for Leber Hereditary Optic Neuropathy, Modifier of

MalaCards organs/tissues related to Leber Hereditary Optic Neuropathy, Modifier of:

40
Eye, Bone Marrow, Bone, Brain, Skin, Retina, Spinal Cord

Publications for Leber Hereditary Optic Neuropathy, Modifier of

Articles related to Leber Hereditary Optic Neuropathy, Modifier of:

(show top 50) (show all 677)
# Title Authors PMID Year
1
Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation? 6 25 57 61
11169561 2001
2
PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy. 6 57
32516135 2020
3
Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. 6 61 25
18771762 2008
4
Leber's hereditary optic neuropathy with dystonia in a Japanese family. 25 54 6
16380132 2006
5
Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. 6 61 25
14735585 2004
6
Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. 61 25 6
8755941 1996
7
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. 25 6 61
8016139 1994
8
An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. 61 6 25
1417830 1992
9
Molecular genetic analysis of a sporadic case of Leber hereditary optic neuropathy. 25 6 61
1734726 1992
10
Heteroplasmy in Leber's hereditary optic neuropathy. 25 6
8240102 1993
11
Cytochrome c oxidase mutations in Leber hereditary optic neuropathy. 61 6 54
8240356 1993
12
Intrafamilial variation in Leber hereditary optic neuropathy revealed by direct mutation analysis. 6 54 61
8448903 1993
13
Cytochrome b mutations in Leber hereditary optic neuropathy. 54 61 6
1764087 1991
14
Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. 61 54 6
1928099 1991
15
The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. 25 6
2039048 1991
16
Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. 25 6
3201231 1988
17
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
18
Primary spinal cord neurodegeneration in Leber hereditary optic neuropathy. 61 6
17620555 2007
19
Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. 61 6
16532388 2006
20
The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees. 61 6
16477364 2006
21
Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. 57 61
16380918 2005
22
A "Fille du Roy" introduced the T14484C Leber hereditary optic neuropathy mutation in French Canadians. 6 61
15954041 2005
23
The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy. 6 54
15505787 2004
24
SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. 61 54 25
15293270 2004
25
Sequence analysis of the mitochondrial genomes from Dutch pedigrees with Leber hereditary optic neuropathy. 6 61
12736867 2003
26
From genotype to phenotype in Leber hereditary optic neuropathy: still more questions than answers. 61 57
12464728 2002
27
Rescue of a mitochondrial deficiency causing Leber Hereditary Optic Neuropathy. 6 61
12402249 2002
28
A case-control study of tobacco and alcohol consumption in Leber hereditary optic neuropathy. 57 61
11124301 2000
29
Predominance of the T14484C mutation in French-Canadian families with Leber hereditary optic neuropathy is due to a founder effect. 6 61
10631164 2000
30
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. 6 61
9150158 1997
31
Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. 6 61
9012411 1997
32
Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy. 61 57
8659512 1996
33
Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. 54 25 61
8644732 1996
34
Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: molecular, biochemical, and clinical findings. 6 61
7573056 1995
35
When does bilateral optic atrophy become Leber hereditary optic neuropathy? 61 6
8213825 1993
36
The two locus control of Leber hereditary optic neuropathy and a high penetrance in Japanese pedigrees. 57 61
8500789 1993
37
Homoplasmic and exclusive ND4 gene mutation in Japanese pedigrees with Leber's disease. 54 6
8449667 1993
38
A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. 6 61
1463007 1992
39
Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy. 61 57
1415219 1992
40
Leber hereditary optic neuropathy: estimation of number of embryonic precursor cells and disease threshold in heterozygous affected females at the X-linked locus. 57 61
1395084 1992
41
Mitochondrial ND-I mutation in Leber hereditary optic neuropathy. 6 61
1550131 1992
42
Mitochondrial DNA mutation and heteroplasmy in type I Leber hereditary optic neuropathy. 61 6
1346348 1992
43
Mitochondrial DNA mutation in an Italian family with Leber hereditary optic neuropathy. 6 61
1937476 1991
44
X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation. 57 61
1896469 1991
45
Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial. 25 61
24525545 2014
46
Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. 25 61
24198293 2013
47
Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy. 25 61
23667621 2013
48
Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy. 25 61
22410442 2012
49
Leber's hereditary optic neuropathy is associated with the T12338C mutation in mitochondrial ND5 gene in six Han Chinese families. 6
21131053 2011
50
Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. 61 25
21112411 2011

Variations for Leber Hereditary Optic Neuropathy, Modifier of

ClinVar genetic disease variations for Leber Hereditary Optic Neuropathy, Modifier of:

6 (show top 50) (show all 54)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MT-ND6 m.14495A>G SNV Pathogenic 9691 rs199476106 MT:14495-14495 MT:14495-14495
2 MT-ND6 m.14482C>A SNV Pathogenic 9693 rs199476108 MT:14482-14482 MT:14482-14482
3 MT-ND5 m.13730G>A SNV Pathogenic 9697 rs387906425 MT:13730-13730 MT:13730-13730
4 MT-ND5 m.12848C>T SNV Pathogenic 9704 rs267606899 MT:12848-12848 MT:12848-12848
5 MT-ND4L m.10663T>C SNV Pathogenic 9707 rs1556423844 MT:10663-10663 MT:10663-10663
6 MT-ND1 m.3733G>A SNV Pathogenic 9736 rs199476125 MT:3733-3733 MT:3733-3733
7 MT-ND6 m.14482C>G SNV Pathogenic 65513 rs199476108 MT:14482-14482 MT:14482-14482
8 MT-ND6 m.14568C>T SNV Pathogenic 65515 rs397515506 MT:14568-14568 MT:14568-14568
9 MT-ND1 m.3700G>A SNV Pathogenic 65519 rs397515508 MT:3700-3700 MT:3700-3700
10 MT-ND1 m.3376G>A SNV Pathogenic 65921 rs397515612 MT:3376-3376 MT:3376-3376
11 MT-ATP6 m.9101T>C SNV Pathogenic 9643 rs199476134 MT:9101-9101 MT:9101-9101
12 MT-CO3 m.9438G>A SNV Pathogenic 9651 rs267606611 MT:9438-9438 MT:9438-9438
13 MT-CO3 m.9804G>A SNV Pathogenic 9652 rs200613617 MT:9804-9804 MT:9804-9804
14 MT-TS1 NC_012920.1:m.7444G>A SNV Pathogenic 9663 rs199474822 MT:7444-7444 MT:7444-7444
15 MT-ND2 m.4640C>A SNV Pathogenic 9718 rs387906426 MT:4640-4640 MT:4640-4640
16 MT-ND1 NC_012920.1:m.3460G>A SNV Pathogenic 9722 rs199476118 MT:3460-3460 MT:3460-3460
17 MT-ND3 m.10237T>C SNV Pathogenic 65508 rs1556423787 MT:10237-10237 MT:10237-10237
18 MT-ND4 m.11253T>C SNV Pathogenic 65509 rs200145866 MT:11253-11253 MT:11253-11253
19 MT-ND5 m.12811T>C SNV Pathogenic 65510 rs199974018 MT:12811-12811 MT:12811-12811
20 MT-ND5 m.13637A>G SNV Pathogenic 65511 rs200855215 MT:13637-13637 MT:13637-13637
21 MT-ND6 m.14325T>C SNV Pathogenic 65512 rs397515505 MT:14325-14325 MT:14325-14325
22 MT-ND6 m.14498T>C SNV Pathogenic 65514 rs869025186 MT:14498-14498 MT:14498-14498
23 MT-ND6 m.14596A>T SNV Pathogenic 9690 rs387906424 MT:14596-14596 MT:14596-14596
24 MT-ND6 m.14279G>A SNV Pathogenic 65516 rs869025187 MT:14279-14279 MT:14279-14279
25 MT-CYB m.14831G>A SNV Pathogenic 65517 rs199795644 MT:14831-14831 MT:14831-14831
26 MT-ND1 m.4025C>T SNV Pathogenic 65520 rs397515509 MT:4025-4025 MT:4025-4025
27 MT-ND1 m.3697G>A SNV Pathogenic 9733 rs199476122 MT:3697-3697 MT:3697-3697
28 MT-CYB m.15812G>A SNV Pathogenic 9675 rs200336777 MT:15812-15812 MT:15812-15812
29 MT-ND6 NC_012920.1:m.14484T>C SNV Pathogenic 9688 rs199476104 MT:14484-14484 MT:14484-14484
30 MT-ND6 m.14459G>A SNV Pathogenic 9689 rs199476105 MT:14459-14459 MT:14459-14459
31 MT-ND4 NC_012920.1:m.11778G>A SNV Pathogenic 9708 rs199476112 MT:11778-11778 MT:11778-11778
32 MT-ND4 m.11777C>A SNV Pathogenic 9711 rs28384199 MT:11777-11777 MT:11777-11777
33 MT-ND5 m.13045A>C SNV Pathogenic 9700 rs267606895 MT:13045-13045 MT:13045-13045
34 MT-ND2 m.5244G>A SNV Pathogenic 9717 rs199476115 MT:5244-5244 MT:5244-5244
35 MT-ND1 m.4160T>C SNV Pathogenic 9723 rs199476119 MT:4160-4160 MT:4160-4160
36 MT-ND5 m.12338T>C SNV Pathogenic 29999 rs201863060 MT:12338-12338 MT:12338-12338
37 MT-ND4 m.11696G>A SNV Pathogenic 9710 rs200873900 MT:11696-11696 MT:11696-11696
38 MT-ND5 m.13042G>A SNV Pathogenic 9703 rs267606898 MT:13042-13042 MT:13042-13042
39 MT-ND1 m.3394T>C SNV Pathogenic 9725 rs41460449 MT:3394-3394 MT:3394-3394
40 MT-ND1 m.4136A>G SNV Pathogenic 9727 rs199476121 MT:4136-4136 MT:4136-4136
41 MT-ND1 m.4171C>A SNV Likely pathogenic 9732 rs28616230 MT:4171-4171 MT:4171-4171
42 MT-ND6 NC_012920.1(MT-ND6):m.14502T>C SNV risk factor 690281 rs201327354 MT:14502-14502 MT:14502-14502
43 PRICKLE3 NM_006150.5(PRICKLE3):c.157C>T (p.Arg53Trp) SNV risk factor 992950 X:49040342-49040342 X:49183889-49183889
44 NDUFS2 NM_004550.4(NDUFS2):c.268G>A (p.Ala90Thr) SNV Likely pathogenic 522715 rs1553249704 1:161176262-161176262 1:161206472-161206472
45 MT-ND5 NC_012920.1:m.13051G>A SNV Likely pathogenic 430689 rs1131692063 MT:13051-13051 MT:13051-13051
46 MT-ND1 m.3635G>A SNV Likely pathogenic 65518 rs397515507 MT:3635-3635 MT:3635-3635
47 MT-CYB m.15257G>A SNV Conflicting interpretations of pathogenicity 9674 rs41518645 MT:15257-15257 MT:15257-15257
48 MT-ND5 m.13708G>A SNV Conflicting interpretations of pathogenicity 9696 rs28359178 MT:13708-13708 MT:13708-13708
49 MT-ND1 m.4216T>C SNV Conflicting interpretations of pathogenicity 9724 rs1599988 MT:4216-4216 MT:4216-4216
50 MT-ND2 m.4917A>G SNV Uncertain significance 9716 rs28357980 MT:4917-4917 MT:4917-4917

UniProtKB/Swiss-Prot genetic disease variations for Leber Hereditary Optic Neuropathy, Modifier of:

73 (show all 18)
# Symbol AA change Variation ID SNP ID
1 MT-ATP6 p.Ile192Thr VAR_000795 rs199476134
2 MT-CO3 p.Gly78Ser VAR_002167 rs267606611
3 MT-CO3 p.Ala200Thr VAR_002168 rs200613617
4 MT-CYB p.Asp171Asn VAR_002197 rs41518645
5 MT-CYB p.Val356Met VAR_002199 rs200336777
6 MT-ND1 p.Ala52Thr VAR_004751 rs199476118
7 MT-ND2 p.Asn150Asp VAR_004755 rs28357980
8 MT-ND2 p.Gly259Ser VAR_004756 rs199476115
9 MT-ND4 p.Arg340His VAR_004760 rs199476112
10 MT-ND4L p.Val65Ala VAR_008397 rs193302933
11 MT-ND5 p.Ala458Thr VAR_004761 rs28359178
12 MT-ND5 p.Gly465Glu VAR_004762 rs387906425
13 MT-ND5 p.Ala171Val VAR_035426 rs267606899
14 MT-ND6 p.Met64Val VAR_004763 rs199476104
15 MT-ND6 p.Gly36Ser VAR_008395 rs397515506
16 MT-ND6 p.Tyr59Cys VAR_008396 rs869025186
17 MT-ND6 p.Met64Ile VAR_008512 rs199476108
18 MT-ND6 p.Leu60Ser VAR_014396 rs199476106

Expression for Leber Hereditary Optic Neuropathy, Modifier of

Search GEO for disease gene expression data for Leber Hereditary Optic Neuropathy, Modifier of.

Pathways for Leber Hereditary Optic Neuropathy, Modifier of

Pathways related to Leber Hereditary Optic Neuropathy, Modifier of according to KEGG:

36
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190

GO Terms for Leber Hereditary Optic Neuropathy, Modifier of

Cellular components related to Leber Hereditary Optic Neuropathy, Modifier of according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.32 PRICKLE3 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC
2 integral component of membrane GO:0016021 10.28 OPA1 NDUFA1 MT-ND6 MT-ND5 MT-ND4L MT-ND4
3 mitochondrion GO:0005739 10.16 OPA1 NDUFS4 NDUFS2 NDUFA1 MYOC MT-ND6
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 9.48 MT-CYB MT-CO1
9 respiratory chain complex IV GO:0045277 9.46 MT-CO3 MT-CO1
10 NADH dehydrogenase complex GO:0030964 9.4 MT-ND4L MT-ND3

Biological processes related to Leber Hereditary Optic Neuropathy, Modifier of according to GeneCards Suite gene sharing:

(show all 14)
# 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 9.73 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 respiratory electron transport chain GO:0022904 9.58 MT-CYB MT-CO3 MT-CO1
7 electron transport coupled proton transport GO:0015990 9.56 MT-ND5 MT-ND4 MT-CYB MT-CO1
8 response to electrical stimulus GO:0051602 9.54 OPA1 MT-CO1
9 ATP synthesis coupled electron transport GO:0042773 9.54 MT-ND5 MT-ND4L MT-ND4
10 negative regulation of intrinsic apoptotic signaling pathway GO:2001243 9.52 OPA1 IVNS1ABP
11 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.49 MT-CO3 MT-CO1
12 response to copper ion GO:0046688 9.48 MT-CYB MT-CO1
13 response to hyperoxia GO:0055093 9.46 MT-CYB MT-ATP6
14 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.32 NDUFS4 NDUFS2 NDUFA1 MT-ND6 MT-ND5 MT-ND4L

Molecular functions related to Leber Hereditary Optic Neuropathy, Modifier of according to GeneCards Suite gene sharing:

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

Sources for Leber Hereditary Optic Neuropathy, Modifier of

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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