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 52 25 58 36 29 6 43 15 39
Lca 12 52 25 15
Leber's Amaurosis 12 52 25
Amaurosis Congenita of Leber 52 58
Congenital Retinal Blindness 52 25
Lhon Plus Disease 12 58
Leber's Disease 12 74
Leber's Congenital Tapetoretinal Degeneration 52
Leber Congenital Tapetoretinal Degeneration 25
Leber's Congenital Tapetoretinal Dysplasia 52
Hereditary Epithelial Dysplasia of Retina 25
Congenital Absence of the Rods and Cones 52
Congenital Amaurosis of Retinal Origin 25
Dysgenesis Neuroepithelialis Retinae 25
Heredoretinopathia Congenitalis 25
Leber's Congenital Amaurosis 12
Amaurosis, Leber Congenital 25
Lebers Congenital Amaurosis 54
Hereditary Retinal Aplasia 25
Leber Abiotrophy 25
Crb 25

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 43 D057130
NCIt 49 C129075
SNOMED-CT 67 193413001
MESH via Orphanet 44 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

Genetics Home Reference : 25 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 10 and leber congenital amaurosis 15. 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 Vitamin A and Pharmaceutical Solutions 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.

NIH Rare Diseases : 52 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.

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

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 327)
# Related Disease Score Top Affiliating Genes
1 leber congenital amaurosis 10 37.0 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 LCA5
2 leber congenital amaurosis 15 36.6 TULP1 SPATA7 RDH12 NMNAT1 LCA5 IQCB1
3 leber congenital amaurosis 13 36.4 TULP1 SPATA7 RPGRIP1 RDH12 LCA5 AIPL1
4 leber congenital amaurosis 12 36.3 SPATA7 RPE65 LCA5 GUCY2D AIPL1
5 leber congenital amaurosis 16 36.3 SPATA7 LCA5 GUCY2D CRB1 AIPL1
6 leber congenital amaurosis 14 36.2 SPATA7 RDH12 LCA5 AIPL1
7 leber congenital amaurosis 1 35.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 NMNAT1
8 senior-loken syndrome 1 35.2 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
9 leber congenital amaurosis 9 34.5 TULP1 SPATA7 RPE65 RDH12 NMNAT1 LCA5
10 leber congenital amaurosis 4 34.4 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 PDE6A
11 leber congenital amaurosis 2 34.2 TULP1 SPATA7 RPE65 RDH12 LCA5 GUCY2D
12 leber congenital amaurosis 6 33.9 TULP1 SPATA7 RPGRIP1 RDH12 LCA5 GUCY2D
13 leber congenital amaurosis / early-onset severe retinal dystrophy 33.9 RPE65 CEP290 AIPL1
14 inherited retinal disorder 33.9 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
15 fundus dystrophy 33.9 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
16 leber congenital amaurosis 8 33.8 TULP1 SPATA7 RPE65 RDH12 LCA5 GUCY2D
17 bardet-biedl syndrome 33.7 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
18 leber congenital amaurosis 7 33.6 SPATA7 RDH12 LCA5 GUCY2D CRB1 AIPL1
19 leber congenital amaurosis 11 33.5 SPATA7 RDH12 LCA5 GUCY2D AIPL1
20 retinitis pigmentosa 33.4 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
21 keratoconus 33.3 TULP1 SPATA7 RPE65 RDH12 NMNAT1 LCA5
22 stargardt disease 33.3 USH2A TULP1 SPATA7 RPE65 RDH12 PDE6A
23 nephronophthisis 14 33.1 IQCB1 CEP290
24 pathologic nystagmus 33.1 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
25 eye disease 33.1 USH2A RPE65 RDH12 NR2E3 IQCB1 GUCY2D
26 achromatopsia 33.1 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
27 retinal disease 33.0 USH2A TULP1 RPGRIP1 RPE65 RDH12 PDE6A
28 cone-rod dystrophy 2 33.0 USH2A TULP1 RPGRIP1 RPE65 RDH12 PDE6A
29 retinal degeneration 32.9 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
30 macular degeneration, age-related, 1 32.8 USH2A RPE65 RDH12 NR2E3 GUCY2D CRB1
31 congenital stationary night blindness 32.6 USH2A TULP1 RPGRIP1 RPE65 RDH12 PDE6A
32 hereditary retinal dystrophy 32.6 USH2A RPE65 GUCY2D CRB1 CEP290 ABCA4
33 joubert syndrome 1 32.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 LCA5
34 yemenite deaf-blind hypopigmentation syndrome 32.6 USH2A RPE65 GUCY2D CRB1 CEP290 AIPL1
35 leber congenital amaurosis 3 32.5 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 LCA5
36 usher syndrome 32.5 USH2A TULP1 RPE65 RDH12 PDE6A LCA5
37 nephronophthisis 32.4 RPGRIP1 IQCB1 CEP290 AHI1
38 cone-rod dystrophy 6 32.3 RPGRIP1 RPE65 PDE6A GUCY2D CRB1 CNGB3
39 leber congenital amaurosis 5 32.3 TULP1 SPATA7 RPGRIP1 RDH12 LCA5 AIPL1
40 severe early-childhood-onset retinal dystrophy 32.1 SPATA7 RPE65 LCA5 CNGB3 ABCA4
41 pseudopapilledema 32.1 RPE65 RDH12 GUCY2D CRB1 CEP290 AIPL1
42 retinoschisis 1, x-linked, juvenile 32.0 RPE65 NR2E3 GRM6 CRB1 CNGB3 ABCA4
43 nonsyndromic retinitis pigmentosa 32.0 USH2A ABCA4
44 meckel syndrome, type 1 32.0 RPGRIP1 IQCB1 CEP290 AHI1
45 retinitis 31.9 USH2A RPGRIP1 RPE65 RDH12 PDE6A CRB1
46 night blindness 31.8 USH2A RPE65 NR2E3 GUCY2D GRM6 ABCA4
47 enhanced s-cone syndrome 31.8 RPE65 NR2E3 CNGB3 AIPL1
48 cone dystrophy 31.8 USH2A RPE65 GUCY2D CNGB3 CEP290 ABCA4
49 choroideremia 31.8 USH2A RPE65 CNGB3 ABCA4
50 cone-rod dystrophy 13 31.7 SPATA7 RPGRIP1 IQCB1

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 17)
# 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 cataract 58 31 frequent (33%) Frequent (79-30%) HP:0000518
5 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
6 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
7 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
8 abnormal electroretinogram 58 31 frequent (33%) Frequent (79-30%) HP:0000512
9 abnormality of neuronal migration 58 31 frequent (33%) Frequent (79-30%) HP:0002269
10 keratoconus 58 31 frequent (33%) Frequent (79-30%) HP:0000563
11 encephalocele 58 31 frequent (33%) Frequent (79-30%) HP:0002084
12 aplasia/hypoplasia of the cerebellar vermis 58 31 frequent (33%) Frequent (79-30%) HP:0006817
13 seizure 31 frequent (33%) HP:0001250
14 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
15 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
16 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
17 seizures 58 Frequent (79-30%)

GenomeRNAi Phenotypes related to Leber Plus Disease according to GeneCards Suite gene sharing:

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.98 GUCY2D
2 Decreased viability GR00055-A-2 9.98 GUCY2D
3 Decreased viability GR00221-A-1 9.98 GUCY2D RPGRIP1
4 Decreased viability GR00221-A-2 9.98 GUCY2D RPGRIP1
5 Decreased viability GR00221-A-3 9.98 GUCY2D
6 Decreased viability GR00221-A-4 9.98 GUCY2D RPGRIP1
7 Decreased viability GR00240-S-1 9.98 GUCY2D
8 Decreased viability GR00249-S 9.98 GUCY2D
9 Decreased viability GR00301-A 9.98 RPGRIP1
10 Decreased viability GR00381-A-1 9.98 RPGRIP1
11 Decreased viability GR00386-A-1 9.98 GUCY2D IQCB1 LCA5 RPGRIP1
12 Decreased viability GR00402-S-2 9.98 GUCY2D LCA5 RDH12 SPATA7
13 Increased the percentage of infected cells GR00402-S-1 8.32 RDH12

MGI Mouse Phenotypes related to Leber Plus Disease:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10.11 ABCA4 AHI1 AIPL1 CEP290 CNGB3 CRB1
2 vision/eye MP:0005391 9.6 ABCA4 AHI1 AIPL1 CDHR1 CEP290 CNGB3
3 pigmentation MP:0001186 9.5 ABCA4 CEP290 CRB1 LCA5 NMNAT1 RPE65

Drugs & Therapeutics for Leber Plus Disease

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

(show all 40)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Vitamin A Approved, Nutraceutical, Vet_approved Phase 2, Phase 3 22737-96-8, 68-26-8, 11103-57-4 9904001 445354
2 Pharmaceutical Solutions Phase 2, Phase 3
3 Lecithin Phase 2, Phase 3
4 Retinol palmitate Phase 2, Phase 3
5 retinol Phase 2, Phase 3
6
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
7
leucovorin Approved Phase 1, Phase 2 58-05-9 6006 143
8
Prednisone Approved, Vet_approved Phase 1, Phase 2 53-03-2 5865
9
Methylprednisolone hemisuccinate Approved Phase 1, Phase 2 2921-57-5
10
Trimethoprim Approved, Vet_approved Phase 1, Phase 2 738-70-5 5578
11
Prednisolone phosphate Approved, Vet_approved Phase 1, Phase 2 302-25-0
12
Polymyxin B Approved, Vet_approved Phase 1, Phase 2 1404-26-8
13 Prednisolone acetate Approved, Vet_approved Phase 1, Phase 2 52-21-1
14
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
15
Adapalene Approved Phase 1, Phase 2 106685-40-9 60164
16
Cysteine Approved, Nutraceutical Phase 1, Phase 2 52-90-4 5862
17
Folic acid Approved, Nutraceutical, Vet_approved Phase 1, Phase 2 59-30-3 6037
18
Prednisolone hemisuccinate Experimental Phase 1, Phase 2 2920-86-7
19 Cytochrome P-450 Enzyme Inhibitors Phase 1, Phase 2
20 Hormones Phase 1, Phase 2
21 Anti-Infective Agents Phase 1, Phase 2
22 Antineoplastic Agents, Hormonal Phase 1, Phase 2
23 Vitamin B Complex Phase 1, Phase 2
24 Hormone Antagonists Phase 1, Phase 2
25 glucocorticoids Phase 1, Phase 2
26 Methylprednisolone Acetate Phase 1, Phase 2
27 Folic Acid Antagonists Phase 1, Phase 2
28 Antiprotozoal Agents Phase 1, Phase 2
29 Folate Phase 1, Phase 2
30 Anti-Bacterial Agents Phase 1, Phase 2
31 Antiparasitic Agents Phase 1, Phase 2
32 Polymyxins Phase 1, Phase 2
33 Vitamin B9 Phase 1, Phase 2
34 Anti-Inflammatory Agents Phase 1, Phase 2
35 Antimalarials Phase 1, Phase 2
36
acetic acid Approved Phase 1 64-19-7 176
37
Retinol acetate Phase 1 127-47-9 10245972
38 Adjuvants, Immunologic Phase 1
39 Protective Agents Phase 1
40 Immunologic Factors Phase 1

Interventional clinical trials:

(show all 32)
# 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 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 Safety and Efficacy of Zuretinol Acetate Oral Solution in Subjects With Inherited Retinal Disease Caused by Mutations in Retinal Pigment Epithelium Protein 65 or Lecithin:Retinol Acyltransferase Not yet recruiting NCT04311112 Phase 2, Phase 3 Placebos;ZA Low dose;ZA high dose
4 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
5 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
6 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
7 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
8 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
9 Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Efficacy of AGN-151587 (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 AGN-151587
10 A Phase 1/2 Dose Escalation Study of Subretinally Injected SAR439483 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D Active, not recruiting NCT03920007 Phase 1, Phase 2 SAR439483;SAR439483 Diluent Solution;Prednisone;Triamcinalone Acetonide;1% Prednisolone;Trimethoprim/polymyxin B
11 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
12 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
13 Autologous Bone Marrow-Derived CD34+, CD133+, and CD271+ Stem Cell Transplantation for Retinitis Pigmentosa Active, not recruiting NCT02709876 Phase 1, Phase 2
14 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
15 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
16 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
17 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
18 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] Active, not recruiting NCT00516477 Phase 1
19 Feasibility and Safety of Adult Human Bone Marrow-Derived Mesenchymal Stem Cells by Intravitreal Injection in Patients With Retinitis Pigmentosa Enrolling by invitation NCT01531348 Phase 1
20 Treatment of Retinitis Pigmentosa and Leber Congenital Amaurosis by Primary Retinal Pigment Epithelial Cells Transplantation Unknown status NCT03566147 Early Phase 1
21 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
22 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
23 Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes Completed NCT00873678
24 Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65 Recruiting NCT02714816
25 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
26 Foundation Fighting Blindness Registry, My Retina Tracker Recruiting NCT02435940
27 Generation of Induced Pluripotent Stem (iPS) Cell Lines From Somatic Cells of Participants With Eye Diseases and From Somatic Cells of Matched Controls Recruiting NCT01432847
28 Visual Information Restoration and Rehabilitation Via Sensory Substitution Technology in Children Recruiting NCT03002597
29 Natural History Study of CEP290-Related Retinal Degeneration Active, not recruiting NCT03396042
30 A Long-Term Follow-Up Study in Subjects Who Received an Adenovirus-Associated Viral Vector Serotype 2 Containing the Human RPE65 Gene (AAV2-hRPE65v2, Voretigene Neparvovec-rzyl) Administered Via Subretinal Injection Active, not recruiting NCT03602820
31 A Post-Authorization, Multicenter, Longitudinal, Observational Safety Registry Study for Patients Treated With Voretigene Neparvovec Active, not recruiting NCT03597399
32 Protocol Study for a Randomized Controlled Trial of the Effects of Transcranial Direct Current Stimulation (tDCS) Associated With Proprioceptive Training in Blind People Not yet recruiting NCT03173105

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
Retina, Eye, Testes, Bone, Cortex, Brain, Thyroid
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 915)
# Title Authors PMID Year
1
Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration. 61 54 6
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. 54 61 6
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. 54 61 6
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 61 6
11389483 2001
9
Null RPGRIP1 alleles in patients with Leber congenital amaurosis. 61 54 6
11283794 2001
10
Mutations in the CRB1 gene cause Leber congenital amaurosis. 6 61 54
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. 61 6 54
9931337 1999
12
RPE65-Related Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy 6 61
31725251 2019
13
Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview 6 61
30285347 2018
14
Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D. 61 6
29559409 2018
15
Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC-E) encoded by GUCY2D. 6 61
29061346 2018
16
A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16). 61 6
25921210 2015
17
Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay. 61 6
24997176 2014
18
Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. 61 6
23307924 2013
19
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
20
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. 6 61
23035049 2013
21
NMNAT1 mutations cause Leber congenital amaurosis. 61 6
22842227 2012
22
Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. 61 6
22842229 2012
23
Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. 6 61
22842230 2012
24
Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. 61 6
22842231 2012
25
Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis. 6 61
21763485 2011
26
Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. 6 61
17554762 2007
27
Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. 6 61
17564974 2007
28
Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis. 61 6
17546029 2007
29
Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. 61 6
17345604 2007
30
Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration. 61 6
17186464 2006
31
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. 61 6
16909394 2006
32
Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis. 61 6
16505055 2006
33
Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. 6 61
16123401 2005
34
Limited proteolysis differentially modulates the stability and subcellular localization of domains of RPGRIP1 that are distinctly affected by mutations in Leber's congenital amaurosis. 6 54
15800011 2005
35
A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. 54 6
15557452 2004
36
Leber Congenital Amaurosis – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61 6
20301475 2004
37
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
38
Novel de novo mutation in CRX gene in a Japanese patient with leber congenital amaurosis. 61 6
12208271 2002
39
A novel locus for Leber congenital amaurosis maps to chromosome 6q. 6 61
10631161 2000
40
Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber's congenital amaurosis. 54 6
9888789 1999
41
De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. 61 6
9537410 1998
42
Mutations in RPE65 cause Leber's congenital amaurosis. 6 54
9326927 1997
43
A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations. 6
25475713 2015
44
Mutations in RD3 are associated with an extremely rare and severe form of early onset retinal dystrophy. 6
22531706 2012
45
Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. 6
19864492 2010
46
Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. 6
19458970 2009
47
Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. 6
19129173 2009
48
Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping. 6
19140180 2009
49
Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. 6
18425797 2008
50
CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. 6
17564967 2007

Variations for Leber Plus Disease

ClinVar genetic disease variations for Leber Plus Disease:

6 (show top 50) (show all 235) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RPE65 NM_000329.3(RPE65):c.1101A>G (p.Arg367=)SNV Pathogenic 427868 rs1553152989 1:68903897-68903897 1:68438214-68438214
2 PDE6A NM_000440.3(PDE6A):c.2027+5G>TSNV Pathogenic 427858 rs794727166 5:149264037-149264037 5:149884474-149884474
3 AHI1 NM_001134831.2(AHI1):c.1912+5G>TSNV Pathogenic 427859 rs1554347012 6:135763715-135763715 6:135442577-135442577
4 CEP290 NM_025114.4(CEP290):c.1910-11T>GSNV Pathogenic 427860 rs1555220638 12:88508350-88508350 12:88114573-88114573
5 CEP290 NM_025114.4(CEP290):c.1623+5G>ASNV Pathogenic 427865 rs1555222073 12:88512415-88512415 12:88118638-88118638
6 RPGRIP1 NM_020366.3(RPGRIP1):c.564A>G (p.Glu188=)SNV Pathogenic 427869 rs574462207 14:21770720-21770720 14:21302561-21302561
7 SPATA7 NM_018418.5(SPATA7):c.19G>A (p.Val7Ile)SNV Pathogenic 427873 rs371609982 14:88852181-88852181 14:88385837-88385837
8 SPATA7 NM_018418.5(SPATA7):c.1215G>T (p.Glu405Asp)SNV Pathogenic 427862 rs768028061 14:88903941-88903941 14:88437597-88437597
9 CRB1 NM_201253.3(CRB1):c.2842T>C (p.Cys948Arg)SNV Pathogenic 427863 rs62645747 1:197398744-197398744 1:197429614-197429614
10 RP2 NM_006915.3(RP2):c.102+3A>CSNV Pathogenic 427871 rs1556313557 X:46696640-46696640 X:46837205-46837205
11 RPGRIP1 NM_020366.3(RPGRIP1):c.2941C>T (p.Arg981Ter)SNV Pathogenic 438163 rs780667159 14:21796628-21796628 14:21328469-21328469
12 CEP290 NM_025114.4(CEP290):c.180+1G>ASNV Pathogenic 461777 rs758593134 12:88534732-88534732 12:88140955-88140955
13 USH2A NM_206933.3(USH2A):c.4957C>T (p.Arg1653Ter)SNV Pathogenic 488733 rs754768875 1:216260091-216260091 1:216086749-216086749
14 LCA5 NM_001122769.3(LCA5):c.1676C>A (p.Ser559Ter)SNV Pathogenic 438152 rs766143193 6:80197139-80197139 6:79487422-79487422
15 LCA5 NM_001122769.3(LCA5):c.838C>T (p.Arg280Ter)SNV Pathogenic 438153 rs866395428 6:80203350-80203350 6:79493633-79493633
16 RPE65 NM_000329.3(RPE65):c.361dup (p.Ser121fs)duplication Pathogenic 559521 rs121918844 1:68910347-68910348 1:68444664-68444665
17 RP2 NM_006915.3(RP2):c.486_490del (p.Gly163fs)deletion Pathogenic 560495 rs1569531639 X:46713292-46713296 X:46853857-46853861
18 RPGRIP1 NM_020366.3(RPGRIP1):c.2440C>T (p.Arg814Ter)SNV Pathogenic 585296 rs759940113 14:21794062-21794062 14:21325903-21325903
19 CRB1 NM_201253.3(CRB1):c.2230C>T (p.Arg744Ter)SNV Pathogenic 635155 rs150412614 1:197396685-197396685 1:197427555-197427555
20 NR2E3 NM_014249.4(NR2E3):c.1171_1172del (p.Phe391fs)deletion Pathogenic 560470 rs574936510 15:72109960-72109961 15:71817619-71817620
21 GUCY2D NM_000180.4(GUCY2D):c.2303G>A (p.Arg768Gln)SNV Pathogenic 560463 rs750889782 17:7917237-7917237 17:8013919-8013919
22 AIPL1 NM_014336.5(AIPL1):c.815G>C (p.Arg272Pro)SNV Pathogenic 635995 17:6329120-6329120 17:6425800-6425800
23 CEP290 NM_025114.4(CEP290):c.5587-1G>CSNV Pathogenic 636006 12:88471122-88471122 12:88077345-88077345
24 CRB1 NM_201253.3(CRB1):c.2680_2684del (p.Asn894fs)deletion Pathogenic 812301 1:197398580-197398584 1:197429450-197429454
25 RPE65 NM_000329.3(RPE65):c.227A>C (p.His76Pro)SNV Pathogenic 812408 1:68912411-68912411 1:68446728-68446728
26 TULP1 NM_003322.6(TULP1):c.1349G>A (p.Trp450Ter)SNV Pathogenic 812438 6:35467904-35467904 6:35500127-35500127
27 TULP1 NM_003322.6(TULP1):c.832_833insTCCC (p.Glu278fs)insertion Pathogenic 812441 6:35473946-35473947 6:35506169-35506170
28 TULP1 NM_003322.6(TULP1):c.781_782insCTCC (p.Lys261fs)insertion Pathogenic 812442 6:35477026-35477027 6:35509249-35509250
29 TULP1 NM_003322.6(TULP1):c.528_529insT (p.Lys177Ter)insertion Pathogenic 812443 6:35477676-35477677 6:35509899-35509900
30 LCA5 NM_001122769.3(LCA5):c.1171A>T (p.Lys391Ter)SNV Pathogenic 812346 6:80198861-80198861 6:79489144-79489144
31 GRM6 NM_000843.3(GRM6):c.(1354+1_1355-1)_(2436+1_2437-1)deldeletion Pathogenic 636145
32 LCA5 NM_001122769.3(LCA5):c.238C>T (p.Arg80Ter)SNV Pathogenic 662038 6:80223411-80223411 6:79513694-79513694
33 CEP290 NM_025114.4(CEP290):c.5788A>T (p.Lys1930Ter)SNV Pathogenic 812264 12:88465625-88465625 12:88071848-88071848
34 AIPL1 NM_014336.5(AIPL1):c.215G>A (p.Trp72Ter)SNV Pathogenic 812218 17:6337300-6337300 17:6433980-6433980
35 AIPL1 NM_014336.5(AIPL1):c.211G>T (p.Val71Phe)SNV Pathogenic 812219 17:6337304-6337304 17:6433984-6433984
36 GUCY2D NM_000180.4(GUCY2D):c.1992T>G (p.His664Gln)SNV Pathogenic 812326 17:7915803-7915803 17:8012485-8012485
37 CRB1 NM_201253.3(CRB1):c.4005+1G>ASNV Pathogenic 812303 1:197411423-197411423 1:197442293-197442293
38 TULP1 NM_003322.6(TULP1):c.1495+2dupduplication Pathogenic 812437 6:35467755-35467756 6:35499978-35499979
39 CFAP410 NM_004928.3(CFAP410):c.643-2A>GSNV Pathogenic 812235 21:45750211-45750211 21:44330328-44330328
40 LCA5 NM_001122769.3(LCA5):c.835C>T (p.Gln279Ter)SNV Pathogenic 968 rs121918165 6:80203353-80203353 6:79493636-79493636
41 CEP290 NM_025114.4(CEP290):c.21G>T (p.Trp7Cys)SNV Pathogenic 1335 rs62635288 12:88535064-88535064 12:88141287-88141287
42 IQCB1 NM_001023570.4(IQCB1):c.424_425del (p.Phe142fs)deletion Pathogenic 1831 rs750962965 3:121527825-121527826 3:121808978-121808979
43 RDH12 NM_152443.3(RDH12):c.164C>T (p.Thr55Met)SNV Pathogenic 805928 14:68191285-68191285 14:67724568-67724568
44 CRB1 NM_201253.3(CRB1):c.455G>A (p.Cys152Tyr)SNV Pathogenic 812296 1:197297936-197297936 1:197328806-197328806
45 RPGRIP1 NM_020366.3(RPGRIP1):c.194G>A (p.Trp65Ter)SNV Pathogenic 4983 rs137853124 14:21762944-21762944 14:21294785-21294785
46 AIPL1 NM_014336.5(AIPL1):c.834G>A (p.Trp278Ter)SNV Pathogenic 5565 rs62637014 17:6329101-6329101 17:6425781-6425781
47 CRB1 NM_201253.3(CRB1):c.3307G>A (p.Gly1103Arg)SNV Pathogenic 5739 rs62636275 1:197404300-197404300 1:197435170-197435170
48 CRB1 NM_201253.3(CRB1):c.4121_4130del (p.Ala1374fs)deletion Pathogenic 5740 rs281865175 1:197446905-197446914 1:197477775-197477784
49 GRM6 NM_000843.4(GRM6):c.1861C>T (p.Arg621Ter)SNV Pathogenic 5840 rs62638214 5:178413394-178413394 5:178986393-178986393
50 RGS9 NM_003835.4(RGS9):c.895T>C (p.Trp299Arg)SNV Pathogenic 5862 rs121908449 17:63193278-63193278 17:65197160-65197160

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

GO Terms for Leber Plus Disease

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.91 USH2A TULP1 SPATA7 RPGRIP1 LCA5 GUCY2D
2 cilium GO:0005929 9.8 TULP1 RPGRIP1 LCA5 CEP290 AHI1
3 ciliary basal body GO:0036064 9.72 USH2A SPATA7 LCA5 CEP290 AHI1
4 centriole GO:0005814 9.67 IQCB1 CEP290 AHI1
5 axoneme GO:0005930 9.65 SPATA7 RPGRIP1 LCA5
6 photoreceptor inner segment GO:0001917 9.55 USH2A TULP1 RDH12 CRB1 AIPL1
7 photoreceptor disc membrane GO:0097381 9.54 PDE6A GUCY2D ABCA4
8 photoreceptor outer segment membrane GO:0042622 9.46 GUCY2D CDHR1
9 MKS complex GO:0036038 9.43 CEP290 AHI1
10 photoreceptor outer segment GO:0001750 9.43 TULP1 SPATA7 IQCB1 GUCY2D CNGB3 ABCA4
11 photoreceptor connecting cilium GO:0032391 9.1 USH2A SPATA7 RPGRIP1 LCA5 IQCB1 CEP290

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 photoreceptor cell maintenance GO:0045494 9.81 USH2A TULP1 SPATA7 RDH12 LCA5 IQCB1
2 retina development in camera-type eye GO:0060041 9.8 TULP1 RPGRIP1 RPE65 PDE6A NR2E3 GRM6
3 response to stimulus GO:0050896 9.77 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12
4 ciliary basal body-plasma membrane docking GO:0097711 9.73 IQCB1 CEP290 AHI1
5 eye photoreceptor cell development GO:0042462 9.72 TULP1 RPGRIP1 NR2E3 CRB1 CEP290
6 retinoid metabolic process GO:0001523 9.69 RPE65 RDH12 ABCA4
7 detection of light stimulus involved in visual perception GO:0050908 9.67 TULP1 RPE65 GRM6 CRB1
8 retina homeostasis GO:0001895 9.63 TULP1 RPE65 AIPL1
9 regulation of rhodopsin mediated signaling pathway GO:0022400 9.61 PDE6A GUCY2D AIPL1
10 retina layer formation GO:0010842 9.58 CRB1 AHI1
11 photoreceptor cell outer segment organization GO:0035845 9.58 CRB1 CDHR1 AHI1
12 hindbrain development GO:0030902 9.57 CEP290 AHI1
13 sensory perception of light stimulus GO:0050953 9.55 USH2A GRM6
14 retina morphogenesis in camera-type eye GO:0060042 9.54 RPE65 CRB1
15 phototransduction, visible light GO:0007603 9.52 AIPL1 ABCA4
16 protein localization to photoreceptor outer segment GO:1903546 9.49 TULP1 SPATA7
17 maintenance of animal organ identity GO:0048496 9.48 USH2A IQCB1
18 visual perception GO:0007601 9.47 USH2A TULP1 SPATA7 RPGRIP1 RPE65 RDH12

Sources for Leber Plus Disease

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