MCID: LBR014
MIFTS: 49

Leber Congenital Amaurosis 4

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

Aliases & Classifications for Leber Congenital Amaurosis 4

MalaCards integrated aliases for Leber Congenital Amaurosis 4:

Name: Leber Congenital Amaurosis 4 57 12 53 75 29 6 15 73
Lca4 57 12 53 75
Amaurosis Congenita of Leber, Type 4 53
Leber Congenital Amaurosis, Type 4 40
Leber Congenital Amaurosis Type 4 53
Retinitis Pigmentosa, Juvenile 57
Retinitis Pigmentosa 73
Cone-Rod Dystrophy 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
keratoconus, which was observed in 1 family, might be secondary to eye rubbing due to lca


HPO:

32
leber congenital amaurosis 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leber Congenital Amaurosis 4

OMIM : 57 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 2 and retinitis pigmentosa. 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 Phototransduction. Affiliated tissues include retina, eye and bone, and related phenotypes are optic disc pallor and cone/cone-rod dystrophy

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 has material basis in mutation in the AIPL1 gene on chromosome 17p13.

UniProtKB/Swiss-Prot : 75 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 family:

Leber Congenital Amaurosis 1 Leber Congenital Amaurosis 2
Leber Congenital Amaurosis 3 Leber Congenital Amaurosis 4
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

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

(show top 50) (show all 81)
# Related Disease Score Top Affiliating Genes
1 cone-rod dystrophy 2 32.4 AIPL1 CRX GUCY2D RPE65
2 retinitis pigmentosa 28.7 AIPL1 CA4 CRX GUCY2D PDE6A RPE65
3 retinal degeneration 28.2 AIPL1 CRX GUCY2D RPE65
4 keratoconus 27.9 AIPL1 CRX GUCY2D RPE65
5 leber congenital amaurosis 27.2 AIPL1 CRX GUCY2D NUB1 PDE6A RPE65
6 spondylometaphyseal dysplasia with cone-rod dystrophy 12.8
7 cone-rod dystrophy 3 12.7
8 cone-rod dystrophy 9 12.7
9 cone-rod dystrophy 7 12.7
10 cone-rod dystrophy and hearing loss 12.7
11 cone-rod dystrophy, x-linked, 1 12.6
12 cone-rod dystrophy, x-linked, 3 12.6
13 cone-rod dystrophy 16 12.6
14 cone-rod dystrophy 5 12.6
15 cone-rod dystrophy 18 12.6
16 cone-rod dystrophy 19 12.6
17 cone-rod dystrophy 20 12.6
18 cone-rod dystrophy 13 12.6
19 cone-rod dystrophy 10 12.6
20 cone-rod dystrophy 11 12.6
21 cone-rod dystrophy 12 12.6
22 cone-rod dystrophy 15 12.6
23 cone-rod dystrophy 6 12.6
24 cone-rod dystrophy 21 12.6
25 cone-rod dystrophy 1 12.5
26 cone-rod dystrophy 8 12.5
27 cone-rod dystrophy 17 12.5
28 cone-rod dystrophy, x-linked, 2 12.5
29 jalili syndrome 12.3
30 cone dystrophy 3 11.9
31 newfoundland rod-cone dystrophy 11.8
32 hypotrichosis, congenital, with juvenile macular dystrophy 11.5
33 leber congenital amaurosis 14 11.4
34 spondylometaphyseal dysplasia, axial 11.3
35 cleft lip-retinopathy syndrome 11.2
36 alstrom syndrome 11.1
37 leber congenital amaurosis 1 11.1
38 bardet-biedl syndrome 1 11.1
39 blue cone monochromacy 11.1
40 leber congenital amaurosis 3 11.1
41 leber congenital amaurosis 10 11.1
42 cone dystrophy 4 11.1
43 bardet-biedl syndrome 11.1
44 retinitis 10.7
45 amelogenesis imperfecta 10.5
46 spondyloepimetaphyseal dysplasia, strudwick type 10.4
47 stargardt disease 10.4
48 danon disease 10.2
49 myopia 10.2
50 megaloblastic anemia 10.2

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
pendular nystagmus
pale optic disc
macular atrophy
poor central vision or blindness from birth
keratoconus (in some patients)
more

Clinical features from OMIM:

604393

Human phenotypes related to Leber Congenital Amaurosis 4:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 optic disc pallor 32 HP:0000543
2 cone/cone-rod dystrophy 32 HP:0000548
3 keratoconus 32 occasional (7.5%) HP:0000563
4 nyctalopia 32 HP:0000662
5 macular atrophy 32 HP:0007401
6 reduced visual acuity 32 HP:0007663
7 undetectable light- and dark-adapted electroretinogram 32 HP:0007688
8 attenuation of retinal blood vessels 32 HP:0007843
9 pendular nystagmus 32 HP:0012043

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.43 PDE6A RPE65 AIPL1 BOC CRX GUCY2D
2 vision/eye MP:0005391 9.1 AIPL1 BOC CRX GUCY2D PDE6A RPE65

Drugs & Therapeutics for Leber Congenital Amaurosis 4

Search Clinical Trials , 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

Anatomical Context for Leber Congenital Amaurosis 4

MalaCards organs/tissues related to Leber Congenital Amaurosis 4:

41
Retina, Eye, Bone, Testes, Skin, Kidney, Pituitary

Publications for Leber Congenital Amaurosis 4

Articles related to Leber Congenital Amaurosis 4:

(show top 50) (show all 1653)
# Title Authors Year
1
Two-year progression analysis of RPE65 autosomal dominant retinitis pigmentosa. ( 29947567 )
2018
2
Characterization of Retinitis Pigmentosa Using Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO). ( 29946494 )
2018
3
Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study. ( 29940899 )
2018
4
Quantification of Macular Microvascular Changes in Patients With Retinitis Pigmentosa Using Optical Coherence Tomography Angiography. ( 29365150 )
2018
5
Optical coherence tomography angiography of the macular microvasculature changes in retinitis pigmentosa. ( 28561452 )
2018
6
Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa. ( 29800053 )
2018
7
Phenotypic expansion and progression of SPATA7-associated retinitis pigmentosa. ( 29411205 )
2018
8
Patients and animal models of CNGI^1-deficient retinitis pigmentosa support gene augmentation approach. ( 29202463 )
2018
9
Simultaneous Presence of Macular Corneal Dystrophy and Retinitis Pigmentosa in Three Members of a Family. ( 29749994 )
2018
10
Targeted Next-Generation Sequencing Reveals Novel RP1 Mutations in Autosomal Recessive Retinitis Pigmentosa. ( 29425069 )
2018
11
Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa. ( 29847794 )
2018
12
Myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications associated with a novel m.5513G>A mutation in the MT-TW gene. ( 29625105 )
2018
13
Coping strategies, vision-related quality of life, and emotional health in managing retinitis pigmentosa: a survey study. ( 29378559 )
2018
14
A novel mutation in RDH5 gene causes retinitis pigmentosa in consanguineous Pakistani family. ( 29892959 )
2018
15
Ultra-widefield imaging in Coats'-type retinitis pigmentosa. ( 29941749 )
2018
16
Targeted Next Generation Sequencing Revealed Novel PRPF31 Mutations in Autosomal Dominant Retinitis Pigmentosa. ( 29957067 )
2018
17
Correlation between aqueous flare and residual visual field area in retinitis pigmentosa. ( 29858180 )
2018
18
Mutation screening of the USH2A gene in retinitis pigmentosa and USHER patients in a Han Chinese population. ( 29899460 )
2018
19
Misdiagnosis of X-linked retinitis pigmentosa in a choroideremia patient with heavily pigmented fundi. ( 29377744 )
2018
20
Variability in clinical phenotypes of PRPF8-linked autosomal dominant retinitis pigmentosa correlates with differential PRPF8/SNRNP200 interactions. ( 29087248 )
2018
21
A novel LRAT mutation affecting splicing in a family with early onset retinitis pigmentosa. ( 29973277 )
2018
22
Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients after Argus II Implantation: an International Study. ( 29940167 )
2018
23
highroad Is a Carboxypetidase Induced by Retinoids to Clear Mutant Rhodopsin-1 in Drosophila Retinitis Pigmentosa Models. ( 29425495 )
2018
24
Expression Profiling Analysis Reveals Key MicroRNA-mRNA Interactions in Early Retinal Degeneration in Retinitis Pigmentosa. ( 29847644 )
2018
25
Eplerenone, a new treatment for an old problem: Retinitis pigmentosa with recalcitrant macular edema. ( 28624313 )
2018
26
Toward the Mutational Landscape of Autosomal Dominant Retinitis Pigmentosa: A Comprehensive Analysis of 258 Spanish Families. ( 29847639 )
2018
27
A splicing mutation in aryl hydrocarbon receptor associated with retinitis pigmentosa. ( 29931334 )
2018
28
Concise Review: Human Induced Pluripotent Stem Cell Models of Retinitis Pigmentosa. ( 29345014 )
2018
29
AAV Gene Augmentation Therapy for CRB1-Associated Retinitis Pigmentosa. ( 29188511 )
2018
30
Intraobserver Repeatability and Interobserver Reproducibility of Ellipsoid Zone Measurements in Retinitis Pigmentosa. ( 29881650 )
2018
31
Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa. ( 29411010 )
2018
32
Design and Development of AAV-based Gene Supplementation Therapies for Achromatopsia and Retinitis Pigmentosa. ( 29188504 )
2018
33
Effect of Oral Valproic Acid vs Placebo for Vision Loss in Patients With Autosomal Dominant Retinitis Pigmentosa: A Randomized Phase 2 Multicenter Placebo-Controlled Clinical Trial. ( 29879277 )
2018
34
Nonclinical Safety Evaluation of scAAV8-<i>RLBP1</i>for Treatment of<i>RLBP1</i>Retinitis Pigmentosa. ( 29359172 )
2018
35
A novel mutation in<i>PRPF31</i>, causative of autosomal dominant retinitis pigmentosa, using the BGISEQ-500 sequencer. ( 29375987 )
2018
36
Rasagiline delays retinal degeneration in a mouse model of retinitis pigmentosa via modulation of Bax/Bcl-2 expression. ( 29372592 )
2018
37
Methodological Insights for Randomized Clinical Trials of Retinitis Pigmentosa: Lessons Learned From a Trial of Valproic Acid. ( 29879289 )
2018
38
Application of empirical Bayes methods to predict the rate of decline in ERG at the individual level among patients with retinitis pigmentosa. ( 29855067 )
2018
39
Targeted Next-Generation Sequencing Reveals a Novel Frameshift Mutation in the MERTK Gene in a Chinese Family with Retinitis Pigmentosa. ( 29437494 )
2018
40
A splice-site variant in FLVCR1 produces retinitis pigmentosa without posterior column ataxia. ( 29192808 )
2018
41
EDI-OCT evaluation of choroidal thickness in retinitis pigmentosa. ( 28604982 )
2018
42
Gene Correction Reverses Ciliopathy and Photoreceptor Loss in iPSC-Derived Retinal Organoids from Retinitis Pigmentosa Patients. ( 29874627 )
2018
43
Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing. ( 29437900 )
2018
44
Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. ( 29305715 )
2018
45
Improved retinal and visual function following panmacular subthreshold diode micropulse laser for retinitis pigmentosa. ( 29449615 )
2018
46
HIF-1I+ stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa. ( 29295858 )
2018
47
Novel Mutations in PRPF31 Causing Retinitis Pigmentosa Identified Using Whole-Exome Sequencing. ( 29260190 )
2017
48
Acute and Protracted Cell Death in Light-Induced Retinal Degeneration in the Canine Model of Rhodopsin Autosomal Dominant Retinitis Pigmentosa. ( 28114588 )
2017
49
Screening for SLC7A14 gene mutations in patients with autosomal recessive or sporadic retinitis pigmentosa. ( 27028480 )
2017
50
A 2 bp deletion in the mitochondrial ATP 6 gene responsible for theA NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. ( 29054413 )
2017

Variations for Leber Congenital Amaurosis 4

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

75
# Symbol AA change Variation ID SNP ID
1 AIPL1 p.Cys239Arg VAR_010139 rs62637012
2 AIPL1 p.Arg270His VAR_067165

ClinVar genetic disease variations for Leber Congenital Amaurosis 4:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 AIPL1 NM_014336.4(AIPL1): c.834G> A (p.Trp278Ter) single nucleotide variant Pathogenic rs62637014 GRCh37 Chromosome 17, 6329101: 6329101
2 AIPL1 NM_014336.4(AIPL1): c.834G> A (p.Trp278Ter) single nucleotide variant Pathogenic rs62637014 GRCh38 Chromosome 17, 6425781: 6425781
3 AIPL1 NM_014336.4(AIPL1): c.1010_1011delAG (p.Glu337Alafs) deletion Pathogenic rs62637016 GRCh37 Chromosome 17, 6328924: 6328925
4 AIPL1 NM_014336.4(AIPL1): c.1010_1011delAG (p.Glu337Alafs) deletion Pathogenic rs62637016 GRCh38 Chromosome 17, 6425604: 6425605
5 AIPL1 NM_014336.4(AIPL1): c.715T> C (p.Cys239Arg) single nucleotide variant Pathogenic rs62637012 GRCh37 Chromosome 17, 6330004: 6330004
6 AIPL1 NM_014336.4(AIPL1): c.715T> C (p.Cys239Arg) single nucleotide variant Pathogenic rs62637012 GRCh38 Chromosome 17, 6426684: 6426684
7 AIPL1 NM_014336.4(AIPL1): c.589G> C (p.Ala197Pro) single nucleotide variant Pathogenic rs62637010 GRCh37 Chromosome 17, 6330254: 6330254
8 AIPL1 NM_014336.4(AIPL1): c.589G> C (p.Ala197Pro) single nucleotide variant Pathogenic rs62637010 GRCh38 Chromosome 17, 6426934: 6426934
9 AIPL1 NM_014336.4(AIPL1): c.617T> A (p.Ile206Asn) single nucleotide variant Pathogenic rs62637011 GRCh37 Chromosome 17, 6330226: 6330226
10 AIPL1 NM_014336.4(AIPL1): c.617T> A (p.Ile206Asn) single nucleotide variant Pathogenic rs62637011 GRCh38 Chromosome 17, 6426906: 6426906
11 AIPL1 NM_014336.4(AIPL1): c.784G> A (p.Gly262Ser) single nucleotide variant Likely pathogenic rs142326926 GRCh37 Chromosome 17, 6329935: 6329935
12 AIPL1 NM_014336.4(AIPL1): c.784G> A (p.Gly262Ser) single nucleotide variant Likely pathogenic rs142326926 GRCh38 Chromosome 17, 6426615: 6426615
13 AIPL1 NM_014336.4(AIPL1): c.401A> T (p.Tyr134Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs16955851 GRCh37 Chromosome 17, 6331702: 6331702
14 AIPL1 NM_014336.4(AIPL1): c.401A> T (p.Tyr134Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs16955851 GRCh38 Chromosome 17, 6428382: 6428382

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 photoreceptor disc membrane GO:0097381 8.62 GUCY2D PDE6A

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

# Name GO ID Score Top Affiliating Genes
1 response to stimulus GO:0050896 9.35 AIPL1 CRX GUCY2D PDE6A RPE65
2 circadian rhythm GO:0007623 9.32 CRX RPE65
3 retina homeostasis GO:0001895 9.26 AIPL1 RPE65
4 regulation of rhodopsin mediated signaling pathway GO:0022400 9.16 GUCY2D PDE6A
5 visual perception GO:0007601 9.02 AIPL1 CRX GUCY2D PDE6A RPE65

Sources for Leber Congenital Amaurosis 4

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10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
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