LCA10
MCID: LBR005
MIFTS: 36

Leber Congenital Amaurosis 10 (LCA10)

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

Aliases & Classifications for Leber Congenital Amaurosis 10

MalaCards integrated aliases for Leber Congenital Amaurosis 10:

Name: Leber Congenital Amaurosis 10 57 12 53 74 29 13 6 15 72
Lca10 57 12 53 74
Amaurosis Congenita of Leber, Type 10 53
Leber Congenital Amaurosis, Type 10 40
Leber Congenital Amaurosis Type 10 53

Characteristics:

HPO:

32
leber congenital amaurosis 10:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110291
MeSH 44 D057130
ICD10 33 H35.5
MedGen 42 C1857821
UMLS 72 C1857821

Summaries for Leber Congenital Amaurosis 10

OMIM : 57 Leber congenital amaurosis is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life (summary by den Hollander et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000). (611755)

MalaCards based summary : Leber Congenital Amaurosis 10, also known as lca10, is related to leber congenital amaurosis and fundus dystrophy. An important gene associated with Leber Congenital Amaurosis 10 is CEP290 (Centrosomal Protein 290). The drug cysteine has been mentioned in the context of this disorder. Affiliated tissues include retina, eye and brain, and related phenotypes are seizures and visual impairment

Disease Ontology : 12 A Leber congenital amaurosis that is characterized by severe infantile-onset cone-rod dystrophy with high hyperopia and severe ERG abnormalities and has material basis in mutation in the CEP290 gene on chromosome 12q21.32.

UniProtKB/Swiss-Prot : 74 Leber congenital amaurosis 10: 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 10

Graphical network of the top 20 diseases related to Leber Congenital Amaurosis 10:



Diseases related to Leber Congenital Amaurosis 10

Symptoms & Phenotypes for Leber Congenital Amaurosis 10

Human phenotypes related to Leber Congenital Amaurosis 10:

32
# Description HPO Frequency HPO Source Accession
1 seizures 32 very rare (1%) HP:0001250
2 visual impairment 32 HP:0000505
3 hyposmia 32 HP:0004409

Clinical features from OMIM:

611755

Drugs & Therapeutics for Leber Congenital Amaurosis 10

Drugs for Leber Congenital Amaurosis 10 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 cysteine Phase 2, Phase 3

Interventional clinical trials:


# 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 QR-110
2 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
3 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 Recruiting NCT03913130 Phase 1, Phase 2 QR-110
4 Natural History Study of CEP290-Related Retinal Degeneration Recruiting NCT03396042

Search NIH Clinical Center for Leber Congenital Amaurosis 10

Genetic Tests for Leber Congenital Amaurosis 10

Genetic tests related to Leber Congenital Amaurosis 10:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 10 29 CEP290

Anatomical Context for Leber Congenital Amaurosis 10

MalaCards organs/tissues related to Leber Congenital Amaurosis 10:

41
Retina, Eye, Brain

Publications for Leber Congenital Amaurosis 10

Articles related to Leber Congenital Amaurosis 10:

(show all 23)
# Title Authors PMID Year
1
Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. 8 71
17554762 2007
2
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. 8 71
16909394 2006
3
Leber Congenital Amaurosis 38 71
20301475 2004
4
Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview 71
30285347 2018
5
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. 71
23105016 2013
6
Genetics and molecular basis of human peroxisome biogenesis disorders. 71
22871920 2012
7
Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations. 8
20805370 2010
8
Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons. 8
17898177 2007
9
Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. 71
17564974 2007
10
CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. 71
17564967 2007
11
Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. 71
17345604 2007
12
In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. 8
16632484 2006
13
Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype. 71
10384394 1999
14
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. 71
9398847 1997
15
Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. 71
9398848 1997
16
Gene editing shows promise in LCA10. 38
30718824 2019
17
Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. 38
30664785 2019
18
Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models. 38
30114557 2018
19
Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA. 38
30195768 2018
20
Basal exon skipping and nonsense-associated altered splicing allows bypassing complete CEP290 loss-of-function in individuals with unusually mild retinal disease. 38
29771326 2018
21
Meta-analysis of GWAS on both Chinese and European populations identifies GPR173 as a novel X chromosome susceptibility gene for SLE. 38
29724251 2018
22
CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10. 38
28109959 2017
23
Mouse Models as Tools to Identify Genetic Pathways for Retinal Degeneration, as Exemplified by Leber's Congenital Amaurosis. 38
27150101 2016

Variations for Leber Congenital Amaurosis 10

ClinVar genetic disease variations for Leber Congenital Amaurosis 10:

6 (show all 30)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 CEP290 NM_025114.3(CEP290): c.1078C> T (p.Arg360Ter) single nucleotide variant Pathogenic rs776645403 12:88519134-88519134 12:88125357-88125357
2 CEP290 NM_025114.3(CEP290): c.4960C> T (p.Gln1654Ter) single nucleotide variant Pathogenic 12:88476860-88476860 12:88083083-88083083
3 CEP290 NM_025114.3(CEP290): c.5668G> T (p.Gly1890Ter) single nucleotide variant Pathogenic rs137852832 12:88471040-88471040 12:88077263-88077263
4 CEP290 NM_025114.3(CEP290): c.2991+1655A> G single nucleotide variant Pathogenic rs281865192 12:88494960-88494960 12:88101183-88101183
5 CEP290 NM_025114.3(CEP290): c.2249T> G (p.Leu750Ter) single nucleotide variant Pathogenic rs137852833 12:88505097-88505097 12:88111320-88111320
6 CEP290 NM_025114.3(CEP290): c.4723A> T (p.Lys1575Ter) single nucleotide variant Pathogenic rs137852834 12:88477713-88477713 12:88083936-88083936
7 CEP290 CEP290, 4-BP DEL, 384TAGA deletion Pathogenic
8 CEP290 CEP290, 5-BP DEL, 1260TAAAG deletion Pathogenic
9 CEP290 NM_025114.3(CEP290): c.1066-1G> A single nucleotide variant Pathogenic rs965522059 12:88519147-88519147 12:88125370-88125370
10 CEP290 NM_025114.3(CEP290): c.1711+1G> A single nucleotide variant Pathogenic rs587783009 12:88512259-88512259 12:88118482-88118482
11 CEP290 NM_025114.3(CEP290): c.2248_2249delTT (p.Leu750Thrfs) deletion Pathogenic rs587783010 12:88505097-88505098 12:88111320-88111321
12 CEP290 NM_025114.3(CEP290): c.3904C> T (p.Gln1302Ter) single nucleotide variant Pathogenic rs587783016 12:88482934-88482934 12:88089157-88089157
13 CEP290 NM_025114.3(CEP290): c.6869dupA (p.Asn2290Lysfs) duplication Pathogenic rs587783017 12:88449444-88449444 12:88055667-88055667
14 CEP290 NM_025114.3(CEP290): c.5344C> T (p.Arg1782Ter) single nucleotide variant Pathogenic rs575767207 12:88472889-88472889 12:88079112-88079112
15 CEP290 NM_025114.3(CEP290): c.4882C> T (p.Gln1628Ter) single nucleotide variant Pathogenic rs376493409 12:88476938-88476938 12:88083161-88083161
16 CEP290 NM_025114.3(CEP290): c.4393C> T (p.Arg1465Ter) single nucleotide variant Pathogenic rs539400286 12:88479860-88479860 12:88086083-88086083
17 CEP290 NM_025114.3(CEP290): c.1429C> T (p.Arg477Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1170451277 12:88513984-88513984 12:88120207-88120207
18 CEP290 NM_025114.3(CEP290): c.4243G> T (p.Glu1415Ter) single nucleotide variant Likely pathogenic rs797044604 12:88480227-88480227 12:88086450-88086450
19 CEP290 NM_025114.3(CEP290): c.4437+1G> A single nucleotide variant Conflicting interpretations of pathogenicity rs760915898 12:88479815-88479815 12:88086038-88086038
20 CEP290 NM_025114.3(CEP290): c.6787A> G (p.Ser2263Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs77778467 12:88452656-88452656 12:88058879-88058879
21 CEP290 NM_025114.3(CEP290): c.4250A> G (p.Gln1417Arg) single nucleotide variant Uncertain significance rs201504946 12:88480220-88480220 12:88086443-88086443
22 CEP290 NM_025114.3(CEP290): c.3660G> T (p.Lys1220Asn) single nucleotide variant Uncertain significance rs201982308 12:88483178-88483178 12:88089401-88089401
23 CEP290 NM_025114.3(CEP290): c.5284C> T (p.Arg1762Cys) single nucleotide variant Uncertain significance rs373307908 12:88472949-88472949 12:88079172-88079172
24 CEP290 NM_025114.3(CEP290): c.6392A> G (p.Glu2131Gly) single nucleotide variant Uncertain significance rs184323010 12:88454737-88454737 12:88060960-88060960
25 CEP290 NM_025114.3(CEP290): c.6629G> A (p.Arg2210His) single nucleotide variant Uncertain significance rs371833544 12:88453691-88453691 12:88059914-88059914
26 CEP290 NM_025114.3(CEP290): c.1670G> A (p.Arg557His) single nucleotide variant Uncertain significance rs184018899 12:88512301-88512301 12:88118524-88118524
27 CEP290 NM_025114.3(CEP290): c.963T> A (p.Asp321Glu) single nucleotide variant Uncertain significance rs774072453 12:88520195-88520195 12:88126418-88126418
28 CEP290 NM_025114.3(CEP290): c.4938A> G (p.Lys1646=) single nucleotide variant Uncertain significance rs371582975 12:88476882-88476882 12:88083105-88083105
29 CEP290 NM_025114.3(CEP290): c.2551G> A (p.Val851Ile) single nucleotide variant Uncertain significance rs764963626 12:88500808-88500808 12:88107031-88107031
30 CEP290 NM_025114.3(CEP290): c.5998A> G (p.Ile2000Val) single nucleotide variant Uncertain significance rs183071230 12:88465084-88465084 12:88071307-88071307

Expression for Leber Congenital Amaurosis 10

Search GEO for disease gene expression data for Leber Congenital Amaurosis 10.

Pathways for Leber Congenital Amaurosis 10

GO Terms for Leber Congenital Amaurosis 10

Cellular components related to Leber Congenital Amaurosis 10 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 centriole GO:0005814 9.16 IQCB1 CEP290
2 centrosome GO:0005813 9.13 MECP2 IQCB1 CEP290
3 photoreceptor connecting cilium GO:0032391 8.62 IQCB1 CEP290

Biological processes related to Leber Congenital Amaurosis 10 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection organization GO:0030030 9.16 IQCB1 CEP290
2 positive regulation of transcription, DNA-templated GO:0045893 9.13 MECP2 IRAK1 CEP290
3 ciliary basal body-plasma membrane docking GO:0097711 8.62 IQCB1 CEP290

Sources for Leber Congenital Amaurosis 10

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
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73 UMLS via Orphanet
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