CRB
MCID: LBR036
MIFTS: 66

Leber Plus Disease (CRB)

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

Aliases & Classifications for Leber Plus Disease

MalaCards integrated aliases for Leber Plus Disease:

Name: Leber Plus Disease 12 58 6 15 37
Leber Congenital Amaurosis 12 20 43 58 36 29 6 44 15 39
Lca 12 20 43 15
Leber's Amaurosis 12 20 43
Leber's Disease 12 74 6
Congenital Absence of the Rods and Cones 20 6
Amaurosis Congenita of Leber 20 58
Congenital Retinal Blindness 20 43
Lhon Plus Disease 12 58
Leber's Congenital Tapetoretinal Degeneration 20
Leber Congenital Tapetoretinal Degeneration 43
Leber's Congenital Tapetoretinal Dysplasia 20
Hereditary Epithelial Dysplasia of Retina 43
Congenital Amaurosis of Retinal Origin 43
Dysgenesis Neuroepithelialis Retinae 43
Heredoretinopathia Congenitalis 43
Leber's Congenital Amaurosis 12
Amaurosis, Leber Congenital 43
Lebers Congenital Amaurosis 54
Hereditary Retinal Aplasia 43
Leber Abiotrophy 43
Crb 43

Characteristics:

Orphanet epidemiological data:

58
leber plus disease
Inheritance: Mitochondrial inheritance; Prevalence: <1/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: normal life expectancy;
leber congenital amaurosis
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare eye diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111754 DOID:14791
KEGG 36 H00837
MeSH 44 D057130
NCIt 50 C129075
SNOMED-CT 67 193413001
MESH via Orphanet 45 D057130
ICD10 via Orphanet 33 H35.5 H47.2
UMLS via Orphanet 72 C0339527
Orphanet 58 ORPHA65 ORPHA99718
UMLS 71 C0339527

Summaries for Leber Plus Disease

MedlinePlus Genetics : 43 Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning in infancy. The visual impairment tends to be stable, although it may worsen very slowly over time.Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). The pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all. Additionally, the clear front covering of the eye (the cornea) may be cone-shaped and abnormally thin, a condition known as keratoconus.A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger. Researchers suspect that this behavior may contribute to deep-set eyes and keratoconus in affected children.In rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. However, researchers are uncertain whether these individuals actually have Leber congenital amaurosis or another syndrome with similar signs and symptoms.At least 13 types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.

MalaCards based summary : Leber Plus Disease, also known as leber congenital amaurosis, is related to leber congenital amaurosis 15 and leber congenital amaurosis 16. An important gene associated with Leber Plus Disease is RPE65 (Retinoid Isomerohydrolase RPE65), and among its related pathways/superpathways are Purine metabolism and Retinol metabolism. The drugs Cysteine and Levoleucovorin have been mentioned in the context of this disorder. Affiliated tissues include Eye, and related phenotypes are abnormality of retinal pigmentation and severely reduced visual acuity

Disease Ontology : 12 A retinal disease that is characterized by nystagmus, sluggish or no pupillary responses, and severe vision loss or blindness.

GARD : 20 Leber congenital amaurosis (LCA) is an eye disorder that primarily affects the retina. People with this condition typically have severe visual impairment beginning in infancy. Other features include photophobia, involuntary movements of the eyes (nystagmus), and extreme farsightedness. The pupils also do not react normally to light. Additionally, the cornea may be cone-shaped and abnormally thin (keratoconus). Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger. Different subtypes have been described. The different subtypes are caused by mutations in different genes. Some of these subtypes are also distinguished by their patterns of vision loss and related eye abnormalities. Treatment includes correction farsightedness and use of low-vision aids when possible.

KEGG : 36 Leber congenital amaurosis (LCA) is a heterogeneous group of severe retinal degenerations, which typically becomes evident in the first year of life. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA is generally inherited in an autosomal recessive manner, and caused by mutations in more than a dozen genes. Several have been demonstrated as potentially efficacious gene therapy targets.

Related Diseases for Leber Plus Disease

Diseases related to Leber Plus Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 309)
# Related Disease Score Top Affiliating Genes
1 leber congenital amaurosis 15 34.5 TULP1 SPATA7 RDH12 RD3 LCA5 IQCB1
2 leber congenital amaurosis 16 34.4 SPATA7 RDH12 RD3 LCA5 IMPDH1 GUCY2D
3 leber congenital amaurosis 12 34.4 SPATA7 RPE65 RDH12 RD3 LCA5 GUCY2D
4 leber congenital amaurosis 13 34.3 TULP1 SPATA7 RDH12 LCA5 IQCB1 AIPL1
5 leber congenital amaurosis 14 34.2 SPATA7 RDH12 LCA5 IQCB1 AIPL1
6 leber congenital amaurosis 1 34.0 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
7 senior-loken syndrome 1 33.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 LCA5
8 leber congenital amaurosis 4 33.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
9 leber congenital amaurosis 2 33.5 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
10 leber congenital amaurosis 9 33.2 TULP1 SPATA7 RPE65 RDH12 NMNAT1 LCA5
11 leber congenital amaurosis 8 33.2 TULP1 SPATA7 RPE65 RDH12 LCA5 IQCB1
12 leber congenital amaurosis 6 33.1 TULP1 SPATA7 RPGRIP1 RDH12 LCA5 IMPDH1
13 leber congenital amaurosis 7 32.9 SPATA7 RDH12 LCA5 IMPDH1 GUCY2D CRX
14 leber optic atrophy and dystonia 32.8 MT-ND6 MT-ND4 MT-ND3
15 fundus dystrophy 32.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
16 keratoconus 32.7 TULP1 SPATA7 RPE65 RDH12 LCA5 IMPDH1
17 leber congenital amaurosis / early-onset severe retinal dystrophy 32.6 RPE65 CEP290 AIPL1
18 leber congenital amaurosis 11 32.6 SPATA7 RDH12 LCA5 IMPDH1 AIPL1
19 stargardt disease 32.4 TULP1 SPATA7 RPE65 RDH12 LCA5 IMPDH1
20 retinitis pigmentosa 32.3 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
21 cone-rod dystrophy 2 32.2 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
22 eye disease 32.1 RPGRIP1 RPE65 RDH12 IQCB1 CRX CRB1
23 pathologic nystagmus 32.0 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 NMNAT1
24 usher syndrome 32.0 TULP1 RPGRIP1 RPE65 RDH12 LCA5 IQCB1
25 achromatopsia 32.0 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
26 leber congenital amaurosis 3 32.0 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
27 nephronophthisis 31.9 SPATA7 RPGRIP1 LCA5 IQCB1 CEP290
28 macular degeneration, age-related, 1 31.9 RPE65 RDH12 GUCY2D CRX CRB1 CEP290
29 retinal degeneration 31.9 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
30 retinal disease 31.9 TULP1 RPGRIP1 RPE65 RDH12 IMPDH1 GUCY2D
31 hereditary retinal dystrophy 31.9 RPE65 GUCY2D CRX CRB1
32 leber congenital amaurosis 5 31.7 TULP1 SPATA7 RPGRIP1 RDH12 RD3 LCA5
33 leber congenital amaurosis 10 31.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
34 joubert syndrome 1 31.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
35 yemenite deaf-blind hypopigmentation syndrome 31.7 RPE65 MT-ND6 GUCY2D CEP290 AIPL1
36 cone-rod dystrophy 6 31.6 RPGRIP1 RPE65 RD3 IQCB1 GUCY2D
37 cone dystrophy 31.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 NMNAT1
38 congenital stationary night blindness 31.5 TULP1 RPGRIP1 RPE65 RDH12 RD3 IQCB1
39 pseudopapilledema 31.5 RPE65 RDH12 GUCY2D CRB1 CEP290 AIPL1
40 severe early-childhood-onset retinal dystrophy 31.5 SPATA7 RPE65 LCA5
41 retinoschisis 1, x-linked, juvenile 31.3 RPE65 GUCY2D CRX CRB1
42 cone-rod dystrophy 13 31.2 SPATA7 RPGRIP1 IQCB1
43 enhanced s-cone syndrome 31.2 RPE65 CRX AIPL1
44 choroideremia 31.2 RPE65 GUCY2D CEP290
45 retinitis 31.2 RPGRIP1 RPE65 IMPDH1 CRB1
46 leber hereditary optic neuropathy, modifier of 31.1 RPE65 MT-ND6 MT-ND4 MT-ND3
47 optic nerve disease 31.1 MT-ND6 MT-ND4 MT-ND3
48 coloboma of macula 31.1 NMNAT1 IQCB1 GDF6 CRX CRB1 CEP290
49 cone-rod dystrophy 12 31.1 GUCY2D AIPL1
50 scotoma 31.1 RPE65 MT-ND6 MT-ND4 GUCY2D CRB1

Graphical network of the top 20 diseases related to Leber Plus Disease:



Diseases related to Leber Plus Disease

Symptoms & Phenotypes for Leber Plus Disease

Human phenotypes related to Leber Plus Disease:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of retinal pigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007703
2 severely reduced visual acuity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001141
3 abnormality of the optic disc 58 31 hallmark (90%) Very frequent (99-80%) HP:0012795
4 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
5 cataract 58 31 frequent (33%) Frequent (79-30%) HP:0000518
6 abnormal electroretinogram 58 31 frequent (33%) Frequent (79-30%) HP:0000512
7 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
8 abnormality of neuronal migration 58 31 frequent (33%) Frequent (79-30%) HP:0002269
9 keratoconus 58 31 frequent (33%) Frequent (79-30%) HP:0000563
10 encephalocele 58 31 frequent (33%) Frequent (79-30%) HP:0002084
11 aplasia/hypoplasia of the cerebellar vermis 58 31 frequent (33%) Frequent (79-30%) HP:0006817
12 seizure 31 frequent (33%) HP:0001250
13 hypotonia 31 frequent (33%) HP:0001252
14 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
15 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
16 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
17 seizures 58 Frequent (79-30%)
18 muscular hypotonia 58 Frequent (79-30%)

MGI Mouse Phenotypes related to Leber Plus Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10.03 AIPL1 CEP290 CRB1 CRX GDF6 GUCY2D
2 vision/eye MP:0005391 9.53 AIPL1 CEP290 CRB1 CRX GDF6 GUCY2D
3 pigmentation MP:0001186 9.5 CEP290 CRB1 CRX LCA5 NMNAT1 RPE65

Drugs & Therapeutics for Leber Plus Disease

Drugs for Leber Plus Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 39)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteine Approved, Nutraceutical Phase 2, Phase 3 52-90-4 5862
2
Levoleucovorin Approved, Investigational Phase 1, Phase 2 68538-85-2 149436
3
Methylprednisolone hemisuccinate Approved Phase 1, Phase 2 2921-57-5
4
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
5
Prednisolone phosphate Approved, Vet_approved Phase 1, Phase 2 302-25-0
6
Prednisone Approved, Vet_approved Phase 1, Phase 2 53-03-2 5865
7 Prednisolone acetate Approved, Vet_approved Phase 1, Phase 2 52-21-1
8
Trimethoprim Approved, Vet_approved Phase 1, Phase 2 738-70-5 5578
9
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
10
Polymyxin B Approved, Vet_approved Phase 1, Phase 2 1404-26-8
11
Folic acid Approved, Nutraceutical, Vet_approved Phase 1, Phase 2 59-30-3 6037
12
Prednisolone hemisuccinate Experimental Phase 1, Phase 2 2920-86-7
13 Pharmaceutical Solutions Phase 1, Phase 2
14 Cytochrome P-450 Enzyme Inhibitors Phase 1, Phase 2
15 Anti-Inflammatory Agents Phase 1, Phase 2
16 Hormones Phase 1, Phase 2
17 Folic Acid Antagonists Phase 1, Phase 2
18 Anti-Infective Agents Phase 1, Phase 2
19 Hormone Antagonists Phase 1, Phase 2
20 Vitamin B Complex Phase 1, Phase 2
21 Antiparasitic Agents Phase 1, Phase 2
22 glucocorticoids Phase 1, Phase 2
23 Antiprotozoal Agents Phase 1, Phase 2
24 Folate Phase 1, Phase 2
25 Vitamin B9 Phase 1, Phase 2
26 Antineoplastic Agents, Hormonal Phase 1, Phase 2
27 Anti-Bacterial Agents Phase 1, Phase 2
28 Methylprednisolone Acetate Phase 1, Phase 2
29 Antimalarials Phase 1, Phase 2
30 Polymyxins Phase 1, Phase 2
31
acetic acid Approved Phase 1 64-19-7 176
32
Vitamin A Approved, Nutraceutical, Vet_approved Phase 1 68-26-8, 11103-57-4 445354
33
Lecithin Experimental Phase 1 8002-43-5
34 Protective Agents Phase 1
35 Immunologic Factors Phase 1
36 retinol Phase 1
37 Retinol palmitate Phase 1
38
Retinol acetate Phase 1 127-47-9 10245972
39 Adjuvants, Immunologic Phase 1

Interventional clinical trials:

(show all 25)
# Name Status NCT ID Phase Drugs
1 Double-masked, Randomized, Controlled, Multiple-dose Study to Evaluate Efficacy, Safety, Tolerability and Syst. Exposure of QR-110 in Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene Active, not recruiting NCT03913143 Phase 2, Phase 3 sepofarsen
2 A Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301] Active, not recruiting NCT00999609 Phase 3
3 An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene Completed NCT03140969 Phase 1, Phase 2 QR-110
4 A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing RPE65 (rAAV2-CB-hRPE65) in Patients With Leber Congenital Amaurosis Type 2 Completed NCT00749957 Phase 1, Phase 2
5 An Open-label, Multi-centre, Phase I/II Dose Escalation Trial of an Adeno Associated Virus Vector for Gene Therapy of Adults And Children With Retinal Dystrophy Associated With Defects in RPE65 (LCA) Completed NCT02781480 Phase 1, Phase 2
6 Prospective Monocentric Open Label Non Randomized Uncontrolled Phase I/II Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65 Completed NCT01496040 Phase 1, Phase 2 rAAV2/4.hRPE65
7 An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (AAV2/2-hRPE65p-hRPE65) for Gene Therapy of Severe Early-onset Retinal Degeneration Completed NCT00643747 Phase 1, Phase 2
8 A Phase 1/2 Dose Escalation Study of Subretinally Injected SAR439483 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D Recruiting NCT03920007 Phase 1, Phase 2 SAR439483;SAR439483 Diluent Solution;Prednisone;Triamcinalone Acetonide;1% Prednisolone;Trimethoprim/polymyxin B
9 Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Efficacy of EDIT-101 in Adult and Pediatric Participants With Leber Congenital Amaurosis Type 10 (LCA10), With Centrosomal Protein 290 (CEP290)-Related Retinal Degeneration Caused by a Compound Heterozygous or Homozygous Mutation Involving c.2991+1655A>G in Intron 26 (IVS26) of the CEP290 Gene ("LCA10-IVS26") Recruiting NCT03872479 Phase 1, Phase 2 EDIT-101
10 An Open-Label, Extension Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to the c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene Active, not recruiting NCT03913130 Phase 1, Phase 2 QR-110
11 A Follow-On Study to Evaluate the Safety of Re-Administration of Adeno-Associated Viral Vector Containing the Gene for Human RPE65 [AAV2-hRPE65v2] to the Contralateral Eye in Subjects With Leber Congenital Amaurosis (LCA) Previously Enrolled in a Phase 1 Study Active, not recruiting NCT01208389 Phase 1, Phase 2
12 Phase 1b Study to Evaluate QLT091001 in Subjects With Leber Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP) Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT) Completed NCT01014052 Phase 1 QLT091001
13 An Open-Label Study to Evaluate the Effects of Repeated Treatments of Oral QLT091001 on Safety and Vision Outcome in Subjects With Leber Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP) Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin: Retinol Acyltransferase (LRAT) (Extension of Study RET IRD 01) Completed NCT01521793 Phase 1 QLT091001
14 A Phase 1 Safety Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 Into the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-101] Completed NCT00516477 Phase 1
15 Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations Completed NCT00821340 Phase 1
16 Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis) Active, not recruiting NCT00481546 Phase 1
17 Treatment of Retinitis Pigmentosa and Leber Congenital Amaurosis by Primary Retinal Pigment Epithelial Cells Transplantation Unknown status NCT03566147 Early Phase 1
18 Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families: Establishment of Genotype-phenotype Correlations and Updating the Clinical Definition of This Retinal Dystrophy Completed NCT02970266
19 Retrospective, Uncontrolled, Multicenter, Case History Study to Determine the Natural History of Visual Function in Subjects With Inherited Retinal Disease (IRD) Caused by Inherited Mutation of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT) Completed NCT02575430
20 Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65 Recruiting NCT02714816
21 Long-term Follow-up Study of Participants Following an Open Label, Multi-centre, Phase I/II Dose Escalation Trial of an Adeno-associated Virus Vector (AAV2/5-OPTIRPE65) for Gene Therapy of Adults and Children With Retinal Dystrophy Owing to Defects in RPE65 (LCA2) Recruiting NCT02946879
22 Natural History of Patients With Inherited Retinal Diseases Due to Mutations in RPE65 Gene Recruiting NCT04525261
23 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
24 Foundation Fighting Blindness Registry, My Retina Tracker Recruiting NCT02435940
25 Natural History Study of CEP290-Related Retinal Degeneration Recruiting NCT03396042

Search NIH Clinical Center for Leber Plus Disease

Cochrane evidence based reviews: leber congenital amaurosis

Genetic Tests for Leber Plus Disease

Genetic tests related to Leber Plus Disease:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 29

Anatomical Context for Leber Plus Disease

MalaCards organs/tissues related to Leber Plus Disease:

40
Eye, Retina, Cortex, Brain, Spinal Cord, Thyroid, Pineal
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Leber Plus Disease:
# Tissue Anatomical CompartmentCell Relevance
1 Eye Retinal Pigmented Epithelium Mature Retinal Pigmented Epithelium Cells Affected by disease, potential therapeutic candidate
2 Eye Retinal Pigmented Epithelium Retinal Pigmented Epithelium Progenitor Cells Affected by disease, potential therapeutic candidate

Publications for Leber Plus Disease

Articles related to Leber Plus Disease:

(show top 50) (show all 1034)
# Title Authors PMID Year
1
Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration. 61 6 54
17962469 2007
2
A G1103R mutation in CRB1 is co-inherited with high hyperopia and Leber congenital amaurosis. 6 61 54
16543197 2006
3
Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis. 61 6 54
16384941 2006
4
Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations. 6 61 54
14962443 2004
5
A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis. 6 61 54
12567265 2002
6
Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin. 54 61 6
12325031 2002
7
Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis. 54 61 6
11528500 2001
8
Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. 54 6 61
11389483 2001
9
Null RPGRIP1 alleles in patients with Leber congenital amaurosis. 6 61 54
11283794 2001
10
Mutations in the CRB1 gene cause Leber congenital amaurosis. 61 54 6
11231775 2001
11
Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function. 54 61 6
9931337 1999
12
Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D. 6 61
29559409 2018
13
Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D. 6 61
29061346 2018
14
A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16). 6 61
25921210 2015
15
Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay. 6 61
24997176 2014
16
Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. 6 61
23307924 2013
17
Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype. 6 61
23308101 2013
18
Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants. 61 6
23035049 2013
19
Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. 6 61
22842229 2012
20
Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. 61 6
22842230 2012
21
NMNAT1 mutations cause Leber congenital amaurosis. 61 6
22842227 2012
22
Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. 6 61
22842231 2012
23
Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis. 61 6
21763485 2011
24
Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. 61 6
17554762 2007
25
Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. 6 61
17564974 2007
26
Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis. 6 61
17546029 2007
27
Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. 6 61
17345604 2007
28
Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration. 6 61
17186464 2006
29
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. 61 6
16909394 2006
30
Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis. 61 6
16505055 2006
31
Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. 6 61
16123401 2005
32
Limited proteolysis differentially modulates the stability and subcellular localization of domains of RPGRIP1 that are distinctly affected by mutations in Leber's congenital amaurosis. 54 6
15800011 2005
33
A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. 6 54
15557452 2004
34
Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. 6 61
15024725 2004
35
Novel de novo mutation in CRX gene in a Japanese patient with leber congenital amaurosis. 6 61
12208271 2002
36
A novel locus for Leber congenital amaurosis maps to chromosome 6q. 6 61
10631161 2000
37
Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber's congenital amaurosis. 54 6
9888789 1999
38
De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. 6 61
9537410 1998
39
Mutations in RPE65 cause Leber's congenital amaurosis. 54 6
9326927 1997
40
PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy. 6
32516135 2020
41
A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations. 6
25475713 2015
42
Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy. 6
22531706 2012
43
Leber's hereditary optic neuropathy is associated with the T12338C mutation in mitochondrial ND5 gene in six Han Chinese families. 6
21131053 2011
44
Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. 6
19864492 2010
45
Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. 6
19458970 2009
46
Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. 6
19129173 2009
47
Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping. 6
19140180 2009
48
Mitochondrial DNA haplogroups M7b1'2 and M8a affect clinical expression of leber hereditary optic neuropathy in Chinese families with the m.11778G-->a mutation. 6
19026397 2008
49
Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. 6
18771762 2008
50
Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. 6
18425797 2008

Variations for Leber Plus Disease

ClinVar genetic disease variations for Leber Plus Disease:

6 (show top 50) (show all 2745)
# 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 LCA5 NM_001122769.3(LCA5):c.1151del (p.Pro384fs) Deletion Pathogenic 966 rs386834252 6:80198881-80198881 6:79489164-79489164
10 LCA5 NM_001122769.3(LCA5):c.1476dup (p.Pro493fs) Duplication Pathogenic 967 rs386834253 6:80197338-80197339 6:79487621-79487622
11 LCA5 NM_001122769.3(LCA5):c.835C>T (p.Gln279Ter) SNV Pathogenic 968 rs121918165 6:80203353-80203353 6:79493636-79493636
12 LCA5 NM_181714.4(LCA5):c.0_-298+211del Deletion Pathogenic 969 6:80246622-80248219 6:79536905-79538502
13 CEP290 NM_025114.4(CEP290):c.2991+1655A>G SNV Pathogenic 1337 rs281865192 12:88494960-88494960 12:88101183-88101183
14 CEP290 NM_025114.4(CEP290):c.2249T>G (p.Leu750Ter) SNV Pathogenic 1338 rs137852833 12:88505097-88505097 12:88111320-88111320
15 CEP290 NM_025114.4(CEP290):c.4723A>T (p.Lys1575Ter) SNV Pathogenic 1339 rs137852834 12:88477713-88477713 12:88083936-88083936
16 CEP290 CEP290, 4-BP DEL, 384TAGA Deletion Pathogenic 1340
17 CEP290 CEP290, 5-BP DEL, 1260TAAAG Deletion Pathogenic 1343
18 RPGRIP1 RPGRIP1, 1-BP DEL, ASP1176 Deletion Pathogenic 4982
19 RPGRIP1 NM_020366.3(RPGRIP1):c.194G>A (p.Trp65Ter) SNV Pathogenic 4983 rs137853124 14:21762944-21762944 14:21294785-21294785
20 RPGRIP1 RPGRIP1, 1-BP INS, GLN893 Insertion Pathogenic 4984
21 RPGRIP1 RPGRIP1, 1-BP DEL, LYS342 Deletion Pathogenic 4985
22 RPGRIP1 RPGRIP1, 3-BP DEL, 3835GAG Deletion Pathogenic 4989
23 CRB1 NM_201253.3(CRB1):c.3299T>G (p.Ile1100Arg) SNV Pathogenic 5734 rs62635659 1:197404292-197404292 1:197435162-197435162
24 CRB1 NM_201253.3(CRB1):c.3997G>T (p.Glu1333Ter) SNV Pathogenic 5735 rs137853136 1:197411414-197411414 1:197442284-197442284
25 CRB1 NM_201253.3(CRB1):c.3307G>A (p.Gly1103Arg) SNV Pathogenic 5739 rs62636275 1:197404300-197404300 1:197435170-197435170
26 CRB1 NM_201253.3(CRB1):c.4121_4130del (p.Ala1374fs) Deletion Pathogenic 5740 rs281865175 1:197446905-197446914 1:197477775-197477784
27 CRX CRX, 2-BP DEL, GLU168 Deletion Pathogenic 7419
28 CRX CRX, 1-BP DEL, GLY217 Deletion Pathogenic 7420
29 CRX NM_000554.6(CRX):c.520del (p.Ala174fs) Deletion Pathogenic 99611 rs281865515 19:48342843-48342843 19:47839586-47839586
30 GUCY2D NM_000180.4(GUCY2D):c.1694T>C (p.Phe565Ser) SNV Pathogenic 9350 rs61749755 17:7912849-7912849 17:8009531-8009531
31 GUCY2D NM_000180.3(GUCY2D):c.389del (p.Pro130Leufs) Deletion Pathogenic 98602 rs61749670 17:7906752-7906752 17:8003434-8003434
32 GUCY2D NM_000180.4(GUCY2D):c.622del (p.Arg208fs) Deletion Pathogenic 98607 rs61749671 17:7906985-7906985 17:8003667-8003667
33 GUCY2D GUCY2D, 1-BP DEL, 2943G Deletion Pathogenic 9358
34 MT-ATP6 m.9101T>C SNV Pathogenic 9643 rs199476134 MT:9101-9101 MT:9101-9101
35 MT-CO3 m.9438G>A SNV Pathogenic 9651 rs267606611 MT:9438-9438 MT:9438-9438
36 MT-CO3 m.9804G>A SNV Pathogenic 9652 rs200613617 MT:9804-9804 MT:9804-9804
37 MT-TS1 NC_012920.1:m.7444G>A SNV Pathogenic 9663 rs199474822 MT:7444-7444 MT:7444-7444
38 IMPDH1 NM_000883.4(IMPDH1):c.849T>G (p.Asn283Lys) SNV Pathogenic 14838 rs121912554 7:128040174-128040174 7:128400120-128400120
39 RPE65 NM_000329.3(RPE65):c.1102T>C (p.Tyr368His) SNV Pathogenic 29870 rs62653011 1:68903896-68903896 1:68438213-68438213
40 RPE65 NM_000329.3(RPE65):c.11+5G>A SNV Pathogenic 98825 rs61751276 1:68915573-68915573 1:68449890-68449890
41 RPE65 NM_000329.3(RPE65):c.907A>T (p.Lys303Ter) SNV Pathogenic 29872 rs61752904 1:68904716-68904716 1:68439033-68439033
42 RPE65 NM_000329.3(RPE65):c.1292A>G (p.Tyr431Cys) SNV Pathogenic 29873 rs62636300 1:68897011-68897011 1:68431328-68431328
43 TULP1 TULP1, IVS2DS, G-A, +1 SNV Pathogenic 7360
44 TULP1 NM_003322.6(TULP1):c.1204G>T (p.Glu402Ter) SNV Pathogenic 30260 rs387906835 6:35471534-35471534 6:35503757-35503757
45 TULP1 NM_003322.6(TULP1):c.1198C>T (p.Arg400Trp) SNV Pathogenic 30261 rs387906836 6:35471540-35471540 6:35503763-35503763
46 TULP1 NM_003322.6(TULP1):c.1102G>T (p.Gly368Trp) SNV Pathogenic 30262 rs387906837 6:35473528-35473528 6:35505751-35505751
47 TULP1 TULP1, 6-BP DUP, NT1593 Duplication Pathogenic 30263
48 GIGYF2 NM_002242.4(KCNJ13):c.496C>T (p.Arg166Ter) SNV Pathogenic 30331 rs387906858 2:233633488-233633488 2:232768778-232768778
49 GIGYF2 NM_002242.4(KCNJ13):c.722T>C (p.Leu241Pro) SNV Pathogenic 30332 rs143607153 2:233633262-233633262 2:232768552-232768552
50 NMNAT1 NM_022787.4(NMNAT1):c.838T>C (p.Ter280Gln) SNV Pathogenic 37132 rs387907290 1:10042757-10042757 1:9982699-9982699

Expression for Leber Plus Disease

Search GEO for disease gene expression data for Leber Plus Disease.

Pathways for Leber Plus Disease

Pathways related to Leber Plus Disease according to KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230
2 Retinol metabolism hsa00830
3 Phototransduction hsa04744

Pathways related to Leber Plus Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.77 RPE65 RDH12 GUCY2D

GO Terms for Leber Plus Disease

Cellular components related to Leber Plus Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.86 TULP1 SPATA7 RPGRIP1 RD3 LCA5 GUCY2D
2 cilium GO:0005929 9.72 TULP1 RPGRIP1 LCA5 IQCB1 CEP290
3 axoneme GO:0005930 9.58 SPATA7 RPGRIP1 LCA5
4 photoreceptor inner segment GO:0001917 9.55 TULP1 RDH12 RD3 CRB1 AIPL1
5 respiratory chain GO:0070469 9.54 MT-ND6 MT-ND4 MT-ND3
6 photoreceptor connecting cilium GO:0032391 9.35 SPATA7 RPGRIP1 LCA5 IQCB1 CEP290
7 photoreceptor outer segment GO:0001750 9.1 TULP1 SPATA7 RD3 IQCB1 GUCY2D CRB1

Biological processes related to Leber Plus Disease according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.95 RPE65 RDH12 MT-ND6 MT-ND4 MT-ND3 IMPDH1
2 response to stimulus GO:0050896 9.81 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
3 retina development in camera-type eye GO:0060041 9.72 TULP1 RPGRIP1 RPE65 RD3 CRB1
4 mitochondrial respiratory chain complex I assembly GO:0032981 9.67 MT-ND6 MT-ND4 MT-ND3
5 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.61 MT-ND6 MT-ND4 MT-ND3
6 retina homeostasis GO:0001895 9.58 TULP1 RPE65 AIPL1
7 eye photoreceptor cell development GO:0042462 9.56 TULP1 RPGRIP1 CRB1 CEP290
8 detection of light stimulus involved in visual perception GO:0050908 9.54 TULP1 RPE65 CRB1
9 retina morphogenesis in camera-type eye GO:0060042 9.51 RPE65 CRB1
10 protein localization to photoreceptor outer segment GO:1903546 9.46 TULP1 SPATA7
11 photoreceptor cell maintenance GO:0045494 9.43 TULP1 SPATA7 RDH12 LCA5 IQCB1 CRB1
12 visual perception GO:0007601 9.32 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3

Molecular functions related to Leber Plus Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NADH dehydrogenase (ubiquinone) activity GO:0008137 8.8 MT-ND6 MT-ND4 MT-ND3

Sources for Leber Plus Disease

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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