LCA2
MCID: LBR012
MIFTS: 38

Leber Congenital Amaurosis 2 (LCA2)

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

Aliases & Classifications for Leber Congenital Amaurosis 2

MalaCards integrated aliases for Leber Congenital Amaurosis 2:

Name: Leber Congenital Amaurosis 2 58 12 54 76 30 13 6 15
Lca2 58 12 54 76
Amaurosis Congenita of Leber, Type 2 77 54
Amaurosis Congenita of Leber Ii 58 12
Leber Congenital Amaurosis, Type Ii 74
Leber Congenital Amaurosis Type Ii 76
Leber Congenital Amaurosis, Type 2 41
Leber Congenital Amaurosis Type 2 54

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive with at least 6 different loci


HPO:

33
leber congenital amaurosis 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leber Congenital Amaurosis 2

OMIM : 58 Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). For a general description and a discussion of genetic heterogeneity of LCA, see 204000. (204100)

MalaCards based summary : Leber Congenital Amaurosis 2, also known as lca2, is related to leber congenital amaurosis. An important gene associated with Leber Congenital Amaurosis 2 is RPE65 (Retinoid Isomerohydrolase RPE65). The drugs Pharmaceutical Solutions and Interleukin 1 Receptor Antagonist Protein have been mentioned in the context of this disorder. Affiliated tissues include eye and retina, and related phenotypes are intellectual disability and cataract

Disease Ontology : 12 A Leber congenital amaurosis that is characterized by night blindness, some transient improvement in vision, and eventual progressive visual loss and has material basis in mutation in the RPE65 gene on chromosome 1.

UniProtKB/Swiss-Prot : 76 Leber congenital amaurosis 2: 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.

Wikipedia : 77 Leber''s congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the... more...

Related Diseases for Leber Congenital Amaurosis 2

Symptoms & Phenotypes for Leber Congenital Amaurosis 2

Human phenotypes related to Leber Congenital Amaurosis 2:

33 (show all 10)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 33 HP:0001249
2 cataract 33 HP:0000518
3 blindness 33 HP:0000618
4 photophobia 33 HP:0000613
5 keratoconus 33 HP:0000563
6 cerebellar vermis hypoplasia 33 HP:0001320
7 pigmentary retinopathy 33 HP:0000580
8 fundus atrophy 33 HP:0001099
9 eye poking 33 HP:0001483
10 decreased light- and dark-adapted electroretinogram amplitude 33 HP:0000654

Symptoms via clinical synopsis from OMIM:

58
Eye:
cataract
blindness
photophobia
keratoconus
pigmentary retinopathy
more
Brain:
hypoplastic cerebellar vermis

Neuro:
mental retardation

Clinical features from OMIM:

204100

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 2:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.5 ATP2B2 BLM HCFC1 ICK REV1 SLC8A1
2 mortality/aging MP:0010768 9.23 BLM GLE1 HCFC1 ICK JPH2 REV1

Drugs & Therapeutics for Leber Congenital Amaurosis 2

Drugs for Leber Congenital Amaurosis 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 1
2 Interleukin 1 Receptor Antagonist Protein Phase 1
3 Mitogens Phase 1
4 Anti-Inflammatory Agents Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis Completed NCT00749957 Phase 1, Phase 2
2 Study of Autologous Conditioned Serum After Anterior Cruciate Ligament Reconstructive Surgery Completed NCT01037738 Phase 1
3 Long-Term Follow-Up Gene Therapy Study for Leber Congenital Amaurosis OPTIRPE65 (Retinal Dystrophy Associated With Defects in RPE65) Recruiting NCT02946879

Search NIH Clinical Center for Leber Congenital Amaurosis 2

Genetic Tests for Leber Congenital Amaurosis 2

Genetic tests related to Leber Congenital Amaurosis 2:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 2 30 RPE65

Anatomical Context for Leber Congenital Amaurosis 2

MalaCards organs/tissues related to Leber Congenital Amaurosis 2:

42
Eye, Retina

Publications for Leber Congenital Amaurosis 2

Articles related to Leber Congenital Amaurosis 2:

# Title Authors Year
1
Investor Outlook: Focus on Upcoming LCA2 Gene Therapy Phase III Results. ( 26390089 )
2015
2
Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results. ( 26684444 )
2015
3
Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2. ( 23474247 )
2013
4
Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations. ( 14962443 )
2004
5
A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. ( 15557452 )
2004
6
A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. ( 12960219 )
2003
7
Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA2). ( 12124981 )
2002
8
Clinical course and visual function in a family with mutations in the RPE65 gene. ( 11786058 )
2002
9
Mutations in RPE65 cause Leber's congenital amaurosis. ( 9326927 )
1997
10
Amaurosis congenita (Leber). ( 13616783 )
1959

Variations for Leber Congenital Amaurosis 2

UniProtKB/Swiss-Prot genetic disease variations for Leber Congenital Amaurosis 2:

76 (show all 26)
# Symbol AA change Variation ID SNP ID
1 RPE65 p.Leu22Pro VAR_017126 rs61751277
2 RPE65 p.Gly40Ser VAR_017127 rs61751281
3 RPE65 p.Arg44Gln VAR_017128 rs61751282
4 RPE65 p.His68Tyr VAR_017129 rs61752866
5 RPE65 p.Arg91Gln VAR_017131 rs61752873
6 RPE65 p.Tyr144Asp VAR_017133 rs61752880
7 RPE65 p.His182Tyr VAR_017134 rs61752884
8 RPE65 p.Val287Phe VAR_017135 rs281865289
9 RPE65 p.Pro363Thr VAR_017138 rs121917744
10 RPE65 p.Ala393Gly VAR_017140 rs62635773
11 RPE65 p.Glu417Gln VAR_017141 rs62636299
12 RPE65 p.Tyr431Cys VAR_018151 rs62636300
13 RPE65 p.Ala434Val VAR_034477 rs34627040
14 RPE65 p.Glu102Lys VAR_060812 rs62642584
15 RPE65 p.Glu148Asp VAR_060813 rs61752882
16 RPE65 p.Asp167Tyr VAR_060814 rs61752883
17 RPE65 p.His182Asn VAR_060815 rs61752884
18 RPE65 p.Tyr239Asp VAR_060816 rs61752896
19 RPE65 p.Cys330Tyr VAR_060818 rs61752908
20 RPE65 p.Ala393Glu VAR_060819
21 RPE65 p.Tyr435Cys VAR_060820 rs62636302
22 RPE65 p.Pro470Leu VAR_060822 rs774211361
23 RPE65 p.Phe70Val VAR_067160
24 RPE65 p.Arg91Pro VAR_067161 rs61752873
25 RPE65 p.His313Arg VAR_067163 rs137594336
26 RPE65 p.Gly40Asp VAR_081684

ClinVar genetic disease variations for Leber Congenital Amaurosis 2:

6 (show top 50) (show all 66)
# Gene Variation Type Significance SNP ID Assembly Location
1 RPE65 NM_000329.2(RPE65): c.700C> T (p.Arg234Ter) single nucleotide variant Pathogenic rs61752895 GRCh37 Chromosome 1, 68905269: 68905269
2 RPE65 NM_000329.2(RPE65): c.700C> T (p.Arg234Ter) single nucleotide variant Pathogenic rs61752895 GRCh38 Chromosome 1, 68439586: 68439586
3 RPE65 NM_000329.2(RPE65): c.271C> T (p.Arg91Trp) single nucleotide variant Pathogenic rs61752871 GRCh37 Chromosome 1, 68910541: 68910541
4 RPE65 NM_000329.2(RPE65): c.271C> T (p.Arg91Trp) single nucleotide variant Pathogenic rs61752871 GRCh38 Chromosome 1, 68444858: 68444858
5 RPE65 NM_000329.2(RPE65): c.394G> A (p.Ala132Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs61752878 GRCh37 Chromosome 1, 68910315: 68910315
6 RPE65 NM_000329.2(RPE65): c.394G> A (p.Ala132Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs61752878 GRCh38 Chromosome 1, 68444632: 68444632
7 RPE65 NM_000329.2(RPE65): c.1543C> T (p.Arg515Trp) single nucleotide variant Pathogenic rs121917745 GRCh37 Chromosome 1, 68895518: 68895518
8 RPE65 NM_000329.2(RPE65): c.1543C> T (p.Arg515Trp) single nucleotide variant Pathogenic rs121917745 GRCh38 Chromosome 1, 68429835: 68429835
9 RPE65 NM_000329.2(RPE65): c.1102T> C (p.Tyr368His) single nucleotide variant Pathogenic rs62653011 GRCh37 Chromosome 1, 68903896: 68903896
10 RPE65 NM_000329.2(RPE65): c.1102T> C (p.Tyr368His) single nucleotide variant Pathogenic rs62653011 GRCh38 Chromosome 1, 68438213: 68438213
11 RPE65 NM_000329.2(RPE65): c.907A> T (p.Lys303Ter) single nucleotide variant Pathogenic rs61752904 GRCh37 Chromosome 1, 68904716: 68904716
12 RPE65 NM_000329.2(RPE65): c.907A> T (p.Lys303Ter) single nucleotide variant Pathogenic rs61752904 GRCh38 Chromosome 1, 68439033: 68439033
13 RPE65 NM_000329.2(RPE65): c.1292A> G (p.Tyr431Cys) single nucleotide variant Pathogenic rs62636300 GRCh37 Chromosome 1, 68897011: 68897011
14 RPE65 NM_000329.2(RPE65): c.1292A> G (p.Tyr431Cys) single nucleotide variant Pathogenic rs62636300 GRCh38 Chromosome 1, 68431328: 68431328
15 RPE65 NM_000329.2(RPE65): c.881A> C (p.Lys294Thr) single nucleotide variant Benign/Likely benign rs61752901 GRCh37 Chromosome 1, 68904742: 68904742
16 RPE65 NM_000329.2(RPE65): c.881A> C (p.Lys294Thr) single nucleotide variant Benign/Likely benign rs61752901 GRCh38 Chromosome 1, 68439059: 68439059
17 RPE65 NM_000329.2(RPE65): c.1067delA (p.Asn356Metfs) deletion Pathogenic rs281865520 GRCh37 Chromosome 1, 68903931: 68903931
18 RPE65 NM_000329.2(RPE65): c.1067delA (p.Asn356Metfs) deletion Pathogenic rs281865520 GRCh38 Chromosome 1, 68438248: 68438248
19 RPE65 NM_000329.2(RPE65): c.11+5G> A single nucleotide variant Pathogenic rs61751276 GRCh37 Chromosome 1, 68915573: 68915573
20 RPE65 NM_000329.2(RPE65): c.11+5G> A single nucleotide variant Pathogenic rs61751276 GRCh38 Chromosome 1, 68449890: 68449890
21 RPE65 NM_000329.2(RPE65): c.1155G> A (p.Thr385=) single nucleotide variant Likely benign rs62653014 GRCh37 Chromosome 1, 68897242: 68897242
22 RPE65 NM_000329.2(RPE65): c.1155G> A (p.Thr385=) single nucleotide variant Likely benign rs62653014 GRCh38 Chromosome 1, 68431559: 68431559
23 RPE65 NM_000329.2(RPE65): c.1301C> T (p.Ala434Val) single nucleotide variant Benign rs34627040 GRCh37 Chromosome 1, 68897002: 68897002
24 RPE65 NM_000329.2(RPE65): c.1301C> T (p.Ala434Val) single nucleotide variant Benign rs34627040 GRCh38 Chromosome 1, 68431319: 68431319
25 RPE65 NM_000329.2(RPE65): c.1302G> C (p.Ala434=) single nucleotide variant Likely benign rs62636301 GRCh37 Chromosome 1, 68897001: 68897001
26 RPE65 NM_000329.2(RPE65): c.1302G> C (p.Ala434=) single nucleotide variant Likely benign rs62636301 GRCh38 Chromosome 1, 68431318: 68431318
27 RPE65 NM_000329.2(RPE65): c.131G> A (p.Arg44Gln) single nucleotide variant Likely pathogenic rs61751282 GRCh37 Chromosome 1, 68912507: 68912507
28 RPE65 NM_000329.2(RPE65): c.131G> A (p.Arg44Gln) single nucleotide variant Likely pathogenic rs61751282 GRCh38 Chromosome 1, 68446824: 68446824
29 RPE65 NM_000329.2(RPE65): c.1338+20A> C single nucleotide variant Benign rs12564647 GRCh37 Chromosome 1, 68896945: 68896945
30 RPE65 NM_000329.2(RPE65): c.1338+20A> C single nucleotide variant Benign rs12564647 GRCh38 Chromosome 1, 68431262: 68431262
31 RPE65 NM_000329.2(RPE65): c.304G> T (p.Glu102Ter) single nucleotide variant Pathogenic/Likely pathogenic rs62642584 GRCh37 Chromosome 1, 68910508: 68910508
32 RPE65 NM_000329.2(RPE65): c.304G> T (p.Glu102Ter) single nucleotide variant Pathogenic/Likely pathogenic rs62642584 GRCh38 Chromosome 1, 68444825: 68444825
33 RPE65 NM_000329.2(RPE65): c.370C> T (p.Arg124Ter) single nucleotide variant Pathogenic rs61752877 GRCh37 Chromosome 1, 68910339: 68910339
34 RPE65 NM_000329.2(RPE65): c.370C> T (p.Arg124Ter) single nucleotide variant Pathogenic rs61752877 GRCh38 Chromosome 1, 68444656: 68444656
35 RPE65 NM_000329.2(RPE65): c.48T> C (p.Phe16=) single nucleotide variant Conflicting interpretations of pathogenicity rs62642581 GRCh37 Chromosome 1, 68914353: 68914353
36 RPE65 NM_000329.2(RPE65): c.48T> C (p.Phe16=) single nucleotide variant Conflicting interpretations of pathogenicity rs62642581 GRCh38 Chromosome 1, 68448670: 68448670
37 RPE65 NM_000329.2(RPE65): c.644-42delT deletion Likely benign rs61752893 GRCh37 Chromosome 1, 68905367: 68905367
38 RPE65 NM_000329.2(RPE65): c.644-42delT deletion Likely benign rs61752893 GRCh38 Chromosome 1, 68439684: 68439684
39 RPE65 NM_000329.2(RPE65): c.644-43delA deletion Likely benign rs61752894 GRCh37 Chromosome 1, 68905368: 68905368
40 RPE65 NM_000329.2(RPE65): c.644-43delA deletion Likely benign rs61752894 GRCh38 Chromosome 1, 68439685: 68439685
41 RPE65 NM_000329.2(RPE65): c.715T> G (p.Tyr239Asp) single nucleotide variant Pathogenic rs61752896 GRCh37 Chromosome 1, 68905254: 68905254
42 RPE65 NM_000329.2(RPE65): c.715T> G (p.Tyr239Asp) single nucleotide variant Pathogenic rs61752896 GRCh38 Chromosome 1, 68439571: 68439571
43 RPE65 NM_000329.2(RPE65): c.95-2A> T single nucleotide variant Pathogenic rs61751279 GRCh37 Chromosome 1, 68912545: 68912545
44 RPE65 NM_000329.2(RPE65): c.95-2A> T single nucleotide variant Pathogenic rs61751279 GRCh38 Chromosome 1, 68446862: 68446862
45 RPE65 NM_000329.2(RPE65): c.978G> T (p.Val326=) single nucleotide variant Likely benign rs61752907 GRCh37 Chromosome 1, 68904645: 68904645
46 RPE65 NM_000329.2(RPE65): c.978G> T (p.Val326=) single nucleotide variant Likely benign rs61752907 GRCh38 Chromosome 1, 68438962: 68438962
47 RPE65 NM_000329.2(RPE65): c.130C> T (p.Arg44Ter) single nucleotide variant Pathogenic/Likely pathogenic rs368088025 GRCh37 Chromosome 1, 68912508: 68912508
48 RPE65 NM_000329.2(RPE65): c.130C> T (p.Arg44Ter) single nucleotide variant Pathogenic/Likely pathogenic rs368088025 GRCh38 Chromosome 1, 68446825: 68446825
49 RPE65 NM_000329.2(RPE65): c.1302G> A (p.Ala434=) single nucleotide variant Benign/Likely benign rs62636301 GRCh37 Chromosome 1, 68897001: 68897001
50 RPE65 NM_000329.2(RPE65): c.1302G> A (p.Ala434=) single nucleotide variant Benign/Likely benign rs62636301 GRCh38 Chromosome 1, 68431318: 68431318

Expression for Leber Congenital Amaurosis 2

Search GEO for disease gene expression data for Leber Congenital Amaurosis 2.

Pathways for Leber Congenital Amaurosis 2

GO Terms for Leber Congenital Amaurosis 2

Biological processes related to Leber Congenital Amaurosis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of cardiac conduction GO:1903779 9.16 ATP2B2 SLC8A1
2 calcium ion homeostasis GO:0055074 8.96 JPH2 SLC8A1
3 calcium ion transport into cytosol GO:0060402 8.62 JPH2 SLC8A1

Molecular functions related to Leber Congenital Amaurosis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.17 ATP2B2 BLM ICK REV1 RPE65 SLC8A1
2 phosphatidylserine binding GO:0001786 8.96 JPH2 RPE65

Sources for Leber Congenital Amaurosis 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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