LCA4
MCID: LBR014
MIFTS: 56

Leber Congenital Amaurosis 4 (LCA4)

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

Aliases & Classifications for Leber Congenital Amaurosis 4

MalaCards integrated aliases for Leber Congenital Amaurosis 4:

Name: Leber Congenital Amaurosis 4 56 12 52 73 29 6 15 71
Lca4 56 12 52 73
Retinitis Pigmentosa, Juvenile 56 29 6
Amaurosis Congenita of Leber, Type 4 52
Leber Congenital Amaurosis, Type 4 39
Leber Congenital Amaurosis Type 4 52
Retinitis Pigmentosa 71
Cone-Rod Dystrophy 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
keratoconus, which was observed in 1 family, might be secondary to eye rubbing due to lca
later onset cord and rp seen in heterozygotes


HPO:

31
leber congenital amaurosis 4:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110332
OMIM 56 604393
OMIM Phenotypic Series 56 PS204000
MeSH 43 D057130
ICD10 32 H35.5
UMLS 71 C0035334 C1858386

Summaries for Leber Congenital Amaurosis 4

OMIM : 56 Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Various intermediate phenotypes between LCA and retinitis pigmentosa are known and are sometimes described as 'early-onset severe rod-cone dystrophy' or 'early-onset retinal degeneration' (Booij et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000; for cone-rod dystrophy, see 120970. (604393)

MalaCards based summary : Leber Congenital Amaurosis 4, also known as lca4, is related to cone-rod dystrophy 12 and cone-rod dystrophy 17. An important gene associated with Leber Congenital Amaurosis 4 is AIPL1 (Aryl Hydrocarbon Receptor Interacting Protein Like 1), and among its related pathways/superpathways are Metabolism of fat-soluble vitamins and Visual Cycle in Retinal Rods. The drugs Sodium citrate and Ranibizumab have been mentioned in the context of this disorder. Affiliated tissues include retina, bone and eye, and related phenotypes are keratoconus and blindness

Disease Ontology : 12 A Leber congenital amaurosis that is characterized by a relatively severe phenotype, with maculopathy and marked bone-spicule pigmentary retinopathy in most and keratoconus and cataract in a large subset and that has material basis in mutation in the AIPL1 gene on chromosome 17p13.

UniProtKB/Swiss-Prot : 73 Leber congenital amaurosis 4: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.

Related Diseases for Leber Congenital Amaurosis 4

Diseases in the Leber Congenital Amaurosis 4 family:

Leber Congenital Amaurosis 1 Leber Congenital Amaurosis 2
Leber Congenital Amaurosis 3 Leber Congenital Amaurosis 5
Leber Congenital Amaurosis 9 Leber Congenital Amaurosis 12
Leber Congenital Amaurosis 10 Leber Congenital Amaurosis 13
Leber Congenital Amaurosis 14 Leber Congenital Amaurosis 6
Leber Congenital Amaurosis 7 Leber Congenital Amaurosis 8
Leber Congenital Amaurosis 11 Leber Congenital Amaurosis 15
Leber Congenital Amaurosis 16 Leber Congenital Amaurosis 17
Leber Congenital Amaurosis 19

Diseases related to Leber Congenital Amaurosis 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 196)
# Related Disease Score Top Affiliating Genes
1 cone-rod dystrophy 12 35.2 GUCY2D AIPL1
2 cone-rod dystrophy 17 35.2 GUCY2D AIPL1
3 cone-rod dystrophy 13 34.9 SPATA7 RPGRIP1
4 cone-rod dystrophy 3 34.7 GUCY2D CRX
5 cone-rod dystrophy 9 34.3 GUCY2D CNGB3
6 cone-rod dystrophy 8 34.1 LCA5 GUCY2D CNGB3 AIPL1
7 newfoundland rod-cone dystrophy 33.6 PRPH2 LRAT
8 leber congenital amaurosis 14 31.7 SPATA7 RDH12 LRAT LCA5 KCNJ13 IMPDH1
9 cone-rod dystrophy 6 31.7 RPGRIP1 RPE65 RD3 PRPH2 PDE6A LRAT
10 cone-rod dystrophy 2 31.5 TULP1 RPGRIP1 RPE65 RDH12 RD3 PRPH2
11 yemenite deaf-blind hypopigmentation syndrome 31.0 RPE65 GUCY2D CRB1 CEP290 AIPL1
12 night blindness 30.9 RPE65 PRPH2 LRAT GUCY2D
13 scotoma 30.3 RPE65 GUCY2D CRB1 CNGB3
14 peripheral retinal degeneration 30.3 PRPH2 IMPDH1
15 nephronophthisis 4 29.8 RPGRIP1 PDE6A
16 color blindness 29.6 RPE65 PDE6A GUCY2D CRX CNGB3 AIPL1
17 retinitis 29.6 RPGRIP1 RPE65 RDH12 PRPH2 PDE6A MERTK
18 cone dystrophy 29.5 RPE65 PRPH2 MERTK GUCY2D CNGB3 CEP290
19 leber congenital amaurosis 10 29.4 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 LCA5
20 bardet-biedl syndrome 29.3 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 PRPH2
21 leber congenital amaurosis 3 29.2 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
22 hereditary retinal dystrophy 28.9 RPE65 PRPH2 MERTK GUCY2D CRX CRB1
23 leber congenital amaurosis 5 28.8 TULP1 SPATA7 RPGRIP1 RDH12 RD3 LRAT
24 usher syndrome 28.7 TULP1 RPE65 RDH12 PRPH2 PDE6A LCA5
25 eye disease 28.4 RPE65 RDH12 PRPH2 GUCY2D CRX CRB1
26 macular degeneration, age-related, 1 28.1 RPE65 RDH12 PRPH2 MERTK LRAT GUCY2D
27 keratoconus 27.7 TULP1 SPATA7 RPE65 RDH12 RD3 LRAT
28 retinal degeneration 27.5 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
29 pathologic nystagmus 27.3 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 LCA5
30 stargardt disease 27.2 TULP1 SPATA7 RPE65 RDH12 PRPH2 PDE6A
31 retinal disease 26.8 TULP1 RPGRIP1 RPE65 RDH12 PRPH2 PDE6A
32 inherited retinal disorder 26.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 PRPH2
33 leber congenital amaurosis 1 26.4 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
34 congenital stationary night blindness 26.2 TULP1 RPGRIP1 RPE65 RDH12 PRPH2 PDE6A
35 achromatopsia 25.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
36 retinitis pigmentosa 24.8 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
37 fundus dystrophy 24.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
38 leber plus disease 24.4 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
39 spondylometaphyseal dysplasia with cone-rod dystrophy 13.1
40 cone-rod dystrophy, x-linked, 1 13.1
41 cone-rod dystrophy and hearing loss 1 13.1
42 cone-rod dystrophy, x-linked, 3 13.1
43 cone-rod dystrophy 16 13.1
44 cone-rod dystrophy 5 13.1
45 cone-rod dystrophy 18 13.0
46 cone-rod dystrophy 20 13.0
47 cone-rod dystrophy 7 13.0
48 cone-rod dystrophy 19 13.0
49 cone-rod dystrophy 15 13.0
50 cone-rod dystrophy 10 13.0

Graphical network of the top 20 diseases related to Leber Congenital Amaurosis 4:



Diseases related to Leber Congenital Amaurosis 4

Symptoms & Phenotypes for Leber Congenital Amaurosis 4

Human phenotypes related to Leber Congenital Amaurosis 4:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 keratoconus 31 occasional (7.5%) HP:0000563
2 blindness 31 HP:0000618
3 reduced visual acuity 31 HP:0007663
4 nyctalopia 31 HP:0000662
5 optic disc pallor 31 HP:0000543
6 cone/cone-rod dystrophy 31 HP:0000548
7 macular atrophy 31 HP:0007401
8 attenuation of retinal blood vessels 31 HP:0007843
9 pendular nystagmus 31 HP:0012043
10 undetectable light- and dark-adapted electroretinogram 31 HP:0007688

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
macular atrophy
pendular nystagmus
pale optic disc
poor central vision or blindness from birth
keratoconus (in some patients)
more

Clinical features from OMIM:

604393

GenomeRNAi Phenotypes related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.17 GUCY2D MERTK
2 Decreased viability GR00055-A-2 10.17 GUCY2D MERTK
3 Decreased viability GR00221-A-1 10.17 GUCY2D MERTK RPGRIP1
4 Decreased viability GR00221-A-2 10.17 GUCY2D RPGRIP1
5 Decreased viability GR00221-A-3 10.17 GUCY2D
6 Decreased viability GR00221-A-4 10.17 GUCY2D MERTK RPGRIP1
7 Decreased viability GR00240-S-1 10.17 GUCY2D
8 Decreased viability GR00249-S 10.17 CRX GRK7 GUCY2D PRPH2
9 Decreased viability GR00301-A 10.17 RPGRIP1
10 Decreased viability GR00381-A-1 10.17 LRAT RPGRIP1
11 Decreased viability GR00386-A-1 10.17 CRX GUCY2D IMPDH1 LCA5 LRAT PRPH2
12 Decreased viability GR00402-S-2 10.17 GUCY2D LCA5 PRPH2 RDH12 SPATA7
13 Increased the percentage of infected cells GR00402-S-1 8.32 RDH12

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 4:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10.09 AIPL1 CEP290 CNGB3 CRB1 CRX GUCY2D
2 vision/eye MP:0005391 9.58 AIPL1 CEP290 CNGB3 CRB1 CRX GUCY2D
3 pigmentation MP:0001186 9.56 CEP290 CRB1 CRX LCA5 MERTK PRPH2

Drugs & Therapeutics for Leber Congenital Amaurosis 4

Drugs for Leber Congenital Amaurosis 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 125)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sodium citrate Approved, Investigational Phase 4 68-04-2
2
Ranibizumab Approved Phase 4 347396-82-1 459903
3
Citric acid Approved, Nutraceutical, Vet_approved Phase 4 77-92-9 311
4 Citrate Phase 4
5 Sildenafil Citrate Phase 4 171599-83-0
6 Phosphodiesterase Inhibitors Phase 4
7 Phosphodiesterase 5 Inhibitors Phase 4
8 Vasodilator Agents Phase 4
9 Immunoglobulins Phase 4
10 Antibodies Phase 4
11 Angiogenesis Inhibitors Phase 4
12 Vardenafil Dihydrochloride Phase 4
13
Tocopherol Approved, Investigational Phase 3 1406-66-2, 54-28-4 14986
14
Lutein Approved, Investigational, Nutraceutical Phase 3 127-40-2 6433159
15
Vitamin D Approved, Nutraceutical, Vet_approved Phase 3 1406-16-2
16
Vitamin E Approved, Nutraceutical, Vet_approved Phase 3 59-02-9 14985
17
Vitamin A Approved, Nutraceutical, Vet_approved Phase 2, Phase 3 22737-96-8, 68-26-8, 11103-57-4 9904001 445354
18 Tocotrienol Investigational Phase 3 6829-55-6
19 Trace Elements Phase 3
20 Vitamins Phase 3
21 Nutrients Phase 3
22 Micronutrients Phase 3
23 Protective Agents Phase 3
24 Calciferol Phase 3
25 Antioxidants Phase 3
26 Tocotrienols Phase 3
27 Tocopherols Phase 3
28 Pharmaceutical Solutions Phase 2, Phase 3
29 Retinol palmitate Phase 2, Phase 3
30 retinol Phase 2, Phase 3
31 Lecithin Phase 2, Phase 3
32 Antihypertensive Agents Phase 3
33 Isopropyl unoprostone Phase 3
34
Dexamethasone acetate Approved, Investigational, Vet_approved Phase 2 1177-87-3
35
Dexamethasone Approved, Investigational, Vet_approved Phase 2 50-02-2 5743
36
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
37
Ciprofloxacin Approved, Investigational Phase 2 85721-33-1 2764
38
Iodine Approved, Investigational Phase 2 7553-56-2 807
39
Povidone Approved Phase 2 9003-39-8
40
Povidone-iodine Approved Phase 2 25655-41-8
41
Acetazolamide Approved, Vet_approved Phase 2 59-66-5 1986
42
Brinzolamide Approved Phase 2 138890-62-7 68844
43
Levodopa Approved Phase 2 59-92-7 6047
44
Carbidopa Approved Phase 2 28860-95-9 34359
45
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
46
Minocycline Approved, Investigational Phase 2 10118-90-8 5281021
47
Hydroxychloroquine Approved Phase 1, Phase 2 118-42-3 3652
48
Adapalene Approved Phase 1, Phase 2 106685-40-9 60164
49
Beta carotene Approved, Nutraceutical Phase 1, Phase 2 7235-40-7
50 Hormones Phase 2

Interventional clinical trials:

(show top 50) (show all 193)
# Name Status NCT ID Phase Drugs
1 A Prospective, Randomized, 3-arm Parallel Trial to Evaluate the Safety and Clinical Effectiveness of 2 Lower Dose Combined PDE5i's vs. Single Maximal Dose PDE5i Treatment Unknown status NCT00498680 Phase 4 Sildenafil, Vardenafil;Sildenafil;Vardenafil;Sildenafil & Vardenafil
2 Role of Capsular Tension Ring in Anterior Capsular Contraction in Retinitis Pigmentosa Patients Completed NCT00717080 Phase 4
3 Correlation of Functional and Structural Outcomes With Serum Antibody Profiles in Patients With Neovascular Age-related Macular Degeneration Treated With Ranibizumab and Healthy Subjects: A Prospective, Controlled Monocenter Trial Completed NCT02843490 Phase 4 Ranibizumab
4 An Integrated Approach With Vardenafil Orodispersible and Cognitive-behavioral Sex Therapy for the Treatment of Erectile Dysfunction (STEDOV) Completed NCT02450188 Phase 4 Vardenafil
5 Randomized Clinical Trial for Retinitis Pigmentosa Completed NCT00346333 Phase 3 Lutein
6 Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa Completed NCT00000114 Phase 3 Vitamin E;Vitamin A
7 Randomized Trial for Retinitis Pigmentosa Completed NCT00000116 Phase 3 Vitamin A;Nutritional Supplement
8 Management of Retinitis Pigmentosa by Wharton's Jelly Derived Mesenchymal Stem Cells: Preliminary Clinical Results Completed NCT04224207 Phase 3
9 A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR) Recruiting NCT03116113 Phase 2, Phase 3
10 The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil on Visual Functions in Patients With Retinitis Pigmentosa Recruiting NCT01680510 Phase 2, Phase 3
11 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
12 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
13 Phase III Clinical Study of UF-021 for Retinitis Pigmentosa - Evaluation for a Comparative Double Masked Placebo Controlled Study Period and a Continuous Administration Period Terminated NCT01786395 Phase 3 UF-021;Placebo
14 Argus® II Retinal Stimulation System Feasibility Protocol Unknown status NCT00407602 Phase 2
15 An Open Labeled Clinical Study to Evaluate the Safety and Efficacy OF Autologous Bone Marrow Derived Mono Nuclear Stem Cell (BMMNCs) in Retinitis Pigmentosa. It is Self Funded (Patients' Own Funding) Clinical Trial Unknown status NCT01914913 Phase 1, Phase 2
16 Prospective Non-randomised Exploratory Study to Assess the Safety and Efficacy of Aflibercept (Eylea) in Cystoid Macular Oedema (CMO) Associated With Retinitis Pigmentosa (RP) Unknown status NCT02661711 Phase 2 Aflibercept
17 Dexamethasone in Retinitis Pigmentosa Cystoid Macular Edema Unknown status NCT02804360 Phase 2
18 A 24 Week Phase Ib/II, Multicenter, Randomized, Controlled, Parallel Group, Dose Ranging Study With a 24 Week Follow-up to Evaluate Safety and Potential Efficacy of 2 Doses (60, 180 µg/ml) of rhNGF Solution vs Vehicle in Patients With RP. Completed NCT02110225 Phase 1, Phase 2 rhNGF 60 µg/ml eye drops solution;rhNGF 180 µg/ml eye drops solution;Placebo
19 Nerve Growth Factor Eye Drops as a Novel Treatment for Vision Loss in Patients With Retinitis Pigmentosa: From Preclinical to Clinical Phase II Trial Completed NCT02609165 Phase 2 rhNGF 180 µg/ml eye drops solution;vehicle eye drops
20 Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa Completed NCT01399515 Phase 2 Valproic Acid
21 An Exploratory Study to Evaluate the Safety of Brimonidine Intravitreal Implant in Patients With Retinitis Pigmentosa Completed NCT00661479 Phase 1, Phase 2 400 µg Brimonidine Tartrate Implant;200 µg Brimonidine Tartrate Implant;100 µg Brimonidine Tartrate Implant
22 A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Autosomal Dominant Retinitis Pigmentosa Completed NCT01233609 Phase 2 Valproic Acid;Placebo
23 A Prospective, Multicenter, Open-Label, Single-Arm Study of the Safety and Tolerability of a Single, Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa (RP) Completed NCT02320812 Phase 1, Phase 2
24 A Phase II/III Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Visual Acuity as the Primary Outcome Completed NCT00447993 Phase 2 NT-501;NT-501
25 A Phase II/III Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Visual Field Sensitivity as the Primary Outcome Completed NCT00447980 Phase 2 NT-501;NT-501
26 Safety Study in Retinal Transplantation for Retinitis Pigmentosa. Completed NCT00345917 Phase 2
27 Phase 2 Study Of Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa Completed NCT01560715 Phase 2
28 Safety Issues of Peribulbar Injection of Umbilical Cord Mesenchymal Stem Cell (UC-MSC) in Patients With Retinitis Pigmentosa Completed NCT04315025 Phase 1, Phase 2
29 Investigation of Effectiveness and Safety of High Dose Docosahexaenoic Acid (DHA) in X-Linked Retinitis Pigmentosa Completed NCT00100230 Phase 2 docosahexaenoic acid OR corn/soy oil placebo
30 Effects of Lutein in Retinitis Pigmentosa Completed NCT00029289 Phase 1, Phase 2 Lutein (10 or 30 mg/day) capsules
31 Pilot Study to Evaluate Oral Minocycline in the Treatment of Cystoid Macular Edema Associated With Retinitis Pigmentosa Completed NCT02140164 Phase 1, Phase 2 Minocycline
32 An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1) Completed NCT01461213 Phase 1, Phase 2 rAAV2.REP1
33 Efficacy and Safety of Intravitreal Ranibizumab (Lucentis®) Injection in the Treatment of Non-leaking Macular Cysts in Patients With Retinal Dystrophy. Completed NCT03763227 Phase 2 Intravitreal ranibizumab (IVR) injection;Carbonic Anhydrase Inhibitor (CAI) therapy
34 The Effect of L-Dopa on the Progression of Retinitis Pigmentosa Recruiting NCT02837640 Phase 2 levodopa-carbidopa
35 Phase 1/2, Safety and Efficacy Trial of BS01, a Recombinant Adeno-Associated Virus Vector Expressing ChronosFP in Patients With Retinitis Pigmentosa Recruiting NCT04278131 Phase 1, Phase 2 BS01
36 First-in-human Phase I/IIa, Open-Label, Prospective Study of the Safety and Tolerability of Subretinally Transplanted Human Retinal Progenitor Cells (hRPC) in Patients With Retinitis Pigmentosa (RP) Recruiting NCT02464436 Phase 1, Phase 2 hRPC
37 The Efficacy and Safety of Oral Minocycline in the Treatment of Retinitis Pigmentosa: An Open-label Clinical Trial Recruiting NCT04068207 Phase 2 Minocycline
38 An Open-label First-in-human Single Ascending Dose Study to Explore Safety, Tolerability and Efficacy of Subretinal Administration of CPK850 Gene Therapy in Patients With Retinitis Pigmentosa Due to Mutations in the Retinaldehyde Binding Protein 1 (RLBP1) Gene Recruiting NCT03374657 Phase 1, Phase 2
39 A Phase 1/2a, Open-Label, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa Recruiting NCT03326336 Phase 1, Phase 2
40 STREAM: A Phase 1/2, Open-label, Safety, Tolerability and Preliminary Efficacy Study of Implantation Into One Eye of hESC-derived RPE in Patients With Retinitis Pigmentosa Due to Monogenic Mutation Recruiting NCT03963154 Phase 1, Phase 2
41 A First-in-Human Study to Evaluate the Safety and Tolerability of QR-421a in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene Recruiting NCT03780257 Phase 1, Phase 2 QR-421a
42 Safety and Efficacy of a Unilateral Subretinal Administration of HORA-PDE6B in Patients With Retinitis Pigmentosa Harbouring Mutations in the PDE6B Gene Leading to a Defect in PDE6ß Expression Recruiting NCT03328130 Phase 1, Phase 2
43 An Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations Recruiting NCT03316560 Phase 1, Phase 2
44 Oral Hydroxychloroquine for Retinitis Pigmentosa Caused by P23H-RHO (Substitution of Proline to Histidine at Codon 23 of the Rhodopsin Protein) Recruiting NCT04120883 Phase 1, Phase 2 Hydroxychloroquine lower dose;Hydroxychloroquine higher dose
45 A Prospective First-In-Human Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa (adRP) Due to the P23H Mutation in the RHO Gene Recruiting NCT04123626 Phase 1, Phase 2 QR-1123
46 Sildenafil for Treatment of Choroidal Ischemia Recruiting NCT04356716 Phase 2 Sildenafil
47 Phase I/IIa, Open-Label, Dose-Escalation Study of Safety and Tolerability of Intravitreal RST-001 in Patients With Advanced Retinitis Pigmentosa (RP) Active, not recruiting NCT02556736 Phase 1, Phase 2 RST-001
48 An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2-.RPGR) for Gene Therapy of Adults and Children With X-linked Retinitis Pigmentosa Owing to Defects in Retinitis Pigmentosa GTPase Regulator (RPGR) Active, not recruiting NCT03252847 Phase 1, Phase 2
49 Photoreceptor Structure in A Phase 2 Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Rates of Change in Cone Spacing and Density Active, not recruiting NCT01530659 Phase 2 NT-501
50 Autologous Bone Marrow-Derived CD34+, CD133+, and CD271+ Stem Cell Transplantation for Retinitis Pigmentosa Active, not recruiting NCT02709876 Phase 1, Phase 2

Search NIH Clinical Center for Leber Congenital Amaurosis 4

Genetic Tests for Leber Congenital Amaurosis 4

Genetic tests related to Leber Congenital Amaurosis 4:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 4 29 AIPL1
2 Retinitis Pigmentosa, Juvenile 29

Anatomical Context for Leber Congenital Amaurosis 4

MalaCards organs/tissues related to Leber Congenital Amaurosis 4:

40
Retina, Bone, Eye, Testes, Bone Marrow, Brain, Pineal

Publications for Leber Congenital Amaurosis 4

Articles related to Leber Congenital Amaurosis 4:

(show all 25)
# Title Authors PMID Year
1
Prevalence of AIPL1 mutations in inherited retinal degenerative disease. 6 61 56
10873396 2000
2
Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis. 61 56 6
10615133 2000
3
Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for gene therapy. 6 56
25596619 2015
4
Leber Congenital Amaurosis – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61 6
20301475 2004
5
A novel locus for Leber congenital amaurosis (LCA4) with anterior keratoconus mapping to chromosome 17p13. 56 61
10711674 2000
6
Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview 6
30285347 2018
7
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. 6
23105016 2013
8
Genetics and molecular basis of human peroxisome biogenesis disorders. 6
22871920 2012
9
The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells. 56
20042464 2010
10
Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors. 56
19299492 2009
11
Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. 56
16272259 2005
12
Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype. 6
10384394 1999
13
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. 6
9398847 1997
14
Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. 6
9398848 1997
15
Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. 56
9326941 1997
16
Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. 56
8944027 1996
17
Retinal Organoids derived from hiPSCs of an AIPL1-LCA Patient Maintain Cytoarchitecture despite Reduced levels of Mutant AIPL1. 61
32214115 2020
18
A new novel nonsense mutation in AIPL1 in a LCA4 family. 61
31576779 2019
19
Aipl1 is required for cone photoreceptor function and survival through the stability of Pde6c and Gc3 in zebrafish. 61
28378769 2017
20
Early alteration of retinal neurons in Aipl1-/- animals. 61
24736053 2014
21
Interaction of aryl hydrocarbon receptor-interacting protein-like 1 with the farnesyl moiety. 61
23737531 2013
22
Structural studies on AIPL1 and its functional interactions with NUB1 to identify key interacting residues in LCA4. 61
24596939 2012
23
Evaluation of Italian patients with leber congenital amaurosis due to AIPL1 mutations highlights the potential applicability of gene therapy. 61
21474771 2011
24
Gene symbol: AIPL1. Disease: LCA4. 61
15991325 2005
25
Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. 61
15365178 2004

Variations for Leber Congenital Amaurosis 4

ClinVar genetic disease variations for Leber Congenital Amaurosis 4:

6 (show top 50) (show all 145) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AIPL1 NM_014336.5(AIPL1):c.265T>C (p.Cys89Arg)SNV Pathogenic 574505 rs1264794214 17:6337250-6337250 17:6433930-6433930
2 SPATA7 NC_000014.9:g.88362113_88425523delinsTGGindel Pathogenic 635162 14:88362113-88425523
3 AIPL1 NM_014336.5(AIPL1):c.211G>T (p.Val71Phe)SNV Pathogenic 812219 17:6337304-6337304 17:6433984-6433984
4 AIPL1 NM_014336.5(AIPL1):c.364G>C (p.Gly122Arg)SNV Pathogenic 870936 17:6331739-6331739 17:6428419-6428419
5 AIPL1 NM_014336.5(AIPL1):c.547G>T (p.Gly183Ter)SNV Pathogenic 848588 17:6330296-6330296 17:6426976-6426976
6 AIPL1 NM_014336.5(AIPL1):c.665G>A (p.Trp222Ter)SNV Pathogenic 916630 17:6330054-6330054 17:6426734-6426734
7 AIPL1 NM_014336.5(AIPL1):c.597dup (p.Lys200fs)duplication Pathogenic 916624 17:6330245-6330246 17:6426925-6426926
8 AIPL1 NM_014336.5(AIPL1):c.582C>G (p.Tyr194Ter)SNV Pathogenic 916623 17:6330261-6330261 17:6426941-6426941
9 AIPL1 NM_014336.5(AIPL1):c.421C>T (p.Gln141Ter)SNV Pathogenic 916622 17:6331682-6331682 17:6428362-6428362
10 AIPL1 NM_014336.5(AIPL1):c.105_106insGTGATCTT (p.His36fs)insertion Pathogenic 916627 17:6337409-6337410 17:6434089-6434090
11 AIPL1 NM_014336.5(AIPL1):c.104_105insG (p.Phe35fs)insertion Pathogenic 916620 17:6337410-6337411 17:6434090-6434091
12 AIPL1 NM_014336.5(AIPL1):c.97_104dup (p.Phe35delinsLeuTer)duplication Pathogenic 916628 17:6337410-6337411 17:6434090-6434091
13 AIPL1 NM_014336.5(AIPL1):c.785-10_786deldeletion Pathogenic 916625 17:6329149-6329160 17:6425829-6425840
14 AIPL1 NM_014336.5(AIPL1):c.466-1G>CSNV Pathogenic 916629 17:6330378-6330378 17:6427058-6427058
15 AIPL1 NM_014336.5(AIPL1):c.96+4A>TSNV Pathogenic 916621 17:6338325-6338325 17:6435005-6435005
16 AIPL1 NC_000017.11:g.6436899deldeletion Pathogenic 916619 17:6340218-6340218 17:6436898-6436898
17 AIPL1 NM_014336.5(AIPL1):c.834G>A (p.Trp278Ter)SNV Pathogenic 5565 rs62637014 17:6329101-6329101 17:6425781-6425781
18 AIPL1 NM_014336.5(AIPL1):c.1008_1009AG[1] (p.Glu337fs)short repeat Pathogenic 5566 rs62637016 17:6328924-6328925 17:6425604-6425605
19 AIPL1 NM_014336.5(AIPL1):c.715T>C (p.Cys239Arg)SNV Pathogenic 5567 rs62637012 17:6330004-6330004 17:6426684-6426684
20 AIPL1 NM_014336.5(AIPL1):c.589G>C (p.Ala197Pro)SNV Pathogenic 65709 rs62637010 17:6330254-6330254 17:6426934-6426934
21 AIPL1 NM_014336.5(AIPL1):c.617T>A (p.Ile206Asn)SNV Pathogenic 65710 rs62637011 17:6330226-6330226 17:6426906-6426906
22 AIPL1 NM_014336.5(AIPL1):c.277-2A>GSNV Pathogenic 99798 rs140808549 17:6331828-6331828 17:6428508-6428508
23 AIPL1 NM_014336.5(AIPL1):c.784G>A (p.Gly262Ser)SNV Pathogenic/Likely pathogenic 65711 rs142326926 17:6329935-6329935 17:6426615-6426615
24 AIPL1 NM_014336.5(AIPL1):c.773G>C (p.Arg258Pro)SNV Likely pathogenic 916626 17:6329946-6329946 17:6426626-6426626
25 AIPL1 NM_014336.5(AIPL1):c.294del (p.Ile99fs)deletion Likely pathogenic 638356 17:6331809-6331809 17:6428489-6428489
26 AIPL1 NM_014336.5(AIPL1):c.98T>C (p.Val33Ala)SNV Conflicting interpretations of pathogenicity 707596 17:6337417-6337417 17:6434097-6434097
27 AIPL1 NM_014336.5(AIPL1):c.267C>T (p.Cys89=)SNV Conflicting interpretations of pathogenicity 95582 rs62653020 17:6337248-6337248 17:6433928-6433928
28 AIPL1 NM_014336.5(AIPL1):c.516T>C (p.His172=)SNV Conflicting interpretations of pathogenicity 95583 rs62637017 17:6330327-6330327 17:6427007-6427007
29 AIPL1 NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu)SNV Conflicting interpretations of pathogenicity 65712 rs62637015 17:6329030-6329030 17:6425710-6425710
30 AIPL1 NM_014336.5(AIPL1):c.765T>C (p.Asp255=)SNV Conflicting interpretations of pathogenicity 99806 rs62637018 17:6329954-6329954 17:6426634-6426634
31 AIPL1 NM_014336.5(AIPL1):c.97-9G>ASNV Conflicting interpretations of pathogenicity 99808 rs140124986 17:6337427-6337427 17:6434107-6434107
32 AIPL1 NM_014336.5(AIPL1):c.937G>T (p.Ala313Ser)SNV Conflicting interpretations of pathogenicity 100585 rs115681466 17:6328998-6328998 17:6425678-6425678
33 AIPL1 NM_014336.5(AIPL1):c.1006G>A (p.Ala336Thr)SNV Conflicting interpretations of pathogenicity 166665 rs143092701 17:6328929-6328929 17:6425609-6425609
34 AIPL1 NM_014336.5(AIPL1):c.33G>C (p.Gly11=)SNV Conflicting interpretations of pathogenicity 771281 17:6338392-6338392 17:6435072-6435072
35 AIPL1 NM_014336.5(AIPL1):c.140C>G (p.Thr47Arg)SNV Conflicting interpretations of pathogenicity 425121 rs150656720 17:6337375-6337375 17:6434055-6434055
36 AIPL1 NM_014336.5(AIPL1):c.401A>T (p.Tyr134Phe)SNV Conflicting interpretations of pathogenicity 196465 rs16955851 17:6331702-6331702 17:6428382-6428382
37 AIPL1 NM_014336.5(AIPL1):c.971G>T (p.Arg324Leu)SNV Conflicting interpretations of pathogenicity 198208 rs150427474 17:6328964-6328964 17:6425644-6425644
38 AIPL1 NM_014336.5(AIPL1):c.-17C>ASNV Conflicting interpretations of pathogenicity 260388 rs188246267 17:6338441-6338441 17:6435121-6435121
39 AIPL1 NM_014336.5(AIPL1):c.234C>T (p.Ser78=)SNV Conflicting interpretations of pathogenicity 99791 rs62635774 17:6337281-6337281 17:6433961-6433961
40 AIPL1 NM_014336.5(AIPL1):c.318G>A (p.Gln106=)SNV Conflicting interpretations of pathogenicity 196462 rs142208422 17:6331785-6331785 17:6428465-6428465
41 AIPL1 NM_014336.5(AIPL1):c.*221G>ASNV Conflicting interpretations of pathogenicity 324597 rs112307858 17:6328559-6328559 17:6425239-6425239
42 AIPL1 NM_014336.5(AIPL1):c.*390G>TSNV Conflicting interpretations of pathogenicity 324595 rs182504714 17:6328390-6328390 17:6425070-6425070
43 AIPL1 NM_014336.5(AIPL1):c.*134G>TSNV Conflicting interpretations of pathogenicity 324607 rs2090068 17:6328646-6328646 17:6425326-6425326
44 AIPL1 NM_014336.5(AIPL1):c.*1178C>TSNV Conflicting interpretations of pathogenicity 324583 rs149460055 17:6327602-6327602 17:6424282-6424282
45 AIPL1 NM_014336.5(AIPL1):c.780C>T (p.His260=)SNV Conflicting interpretations of pathogenicity 324613 rs145304845 17:6329939-6329939 17:6426619-6426619
46 AIPL1 NM_014336.5(AIPL1):c.*1237C>TSNV Conflicting interpretations of pathogenicity 324580 rs139074266 17:6327543-6327543 17:6424223-6424223
47 AIPL1 NM_014336.5(AIPL1):c.*824G>CSNV Conflicting interpretations of pathogenicity 324590 rs145706166 17:6327956-6327956 17:6424636-6424636
48 AIPL1 NM_014336.5(AIPL1):c.*188G>ASNV Conflicting interpretations of pathogenicity 324598 rs1317185 17:6328592-6328592 17:6425272-6425272
49 AIPL1 NM_014336.5(AIPL1):c.737A>C (p.Tyr246Ser)SNV Conflicting interpretations of pathogenicity 324614 rs138585919 17:6329982-6329982 17:6426662-6426662
50 AIPL1 NM_014336.5(AIPL1):c.642+14G>ASNV Conflicting interpretations of pathogenicity 324615 rs188779461 17:6330187-6330187 17:6426867-6426867

UniProtKB/Swiss-Prot genetic disease variations for Leber Congenital Amaurosis 4:

73
# Symbol AA change Variation ID SNP ID
1 AIPL1 p.Cys239Arg VAR_010139 rs62637012
2 AIPL1 p.Arg270His VAR_067165

Expression for Leber Congenital Amaurosis 4

Search GEO for disease gene expression data for Leber Congenital Amaurosis 4.

Pathways for Leber Congenital Amaurosis 4

GO Terms for Leber Congenital Amaurosis 4

Cellular components related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.86 TULP1 SPATA7 RPGRIP1 RD3 PRPH2 LCA5
2 cilium GO:0005929 9.73 TULP1 RPGRIP1 LCA5 CEP290
3 ciliary basal body GO:0036064 9.58 SPATA7 LCA5 CEP290
4 axoneme GO:0005930 9.54 SPATA7 RPGRIP1 LCA5
5 photoreceptor disc membrane GO:0097381 9.5 PDE6A GUCY2D GRK7
6 photoreceptor connecting cilium GO:0032391 9.46 SPATA7 RPGRIP1 LCA5 CEP290
7 photoreceptor inner segment GO:0001917 9.43 TULP1 RDH12 RD3 PRPH2 CRB1 AIPL1
8 photoreceptor outer segment GO:0001750 9.17 TULP1 SPATA7 RD3 PRPH2 MERTK GUCY2D

Biological processes related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 response to stimulus GO:0050896 9.8 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
2 retina development in camera-type eye GO:0060041 9.76 TULP1 RPGRIP1 RPE65 RD3 PRPH2 PDE6A
3 retinoid metabolic process GO:0001523 9.69 RPE65 RDH12 LRAT
4 regulation of rhodopsin mediated signaling pathway GO:0022400 9.67 PDE6A GUCY2D GRK7 AIPL1
5 photoreceptor cell maintenance GO:0045494 9.65 TULP1 SPATA7 RDH12 LCA5 CRB1
6 retinol metabolic process GO:0042572 9.63 RPE65 RDH12 LRAT
7 eye photoreceptor cell development GO:0042462 9.62 TULP1 RPGRIP1 CRB1 CEP290
8 retina homeostasis GO:0001895 9.61 TULP1 RPE65 AIPL1
9 detection of light stimulus involved in visual perception GO:0050908 9.58 TULP1 RPE65 CRB1
10 retina morphogenesis in camera-type eye GO:0060042 9.52 RPE65 CRB1
11 visual perception GO:0007601 9.5 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
12 vitamin A metabolic process GO:0006776 9.49 RPE65 LRAT
13 protein localization to photoreceptor outer segment GO:1903546 9.48 TULP1 SPATA7

Sources for Leber Congenital Amaurosis 4

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
Content
Loading form....