LCA10
MCID: LBR005
MIFTS: 44

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 56 12 52 73 29 13 6 15 71
Lca10 56 12 52 73
Amaurosis Congenita of Leber, Type 10 52
Leber Congenital Amaurosis, Type 10 39
Leber Congenital Amaurosis Type 10 52

Characteristics:

HPO:

31
leber congenital amaurosis 10:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110291
OMIM 56 611755
OMIM Phenotypic Series 56 PS204000
MeSH 43 D057130
ICD10 32 H35.5
MedGen 41 C1857821
UMLS 71 C1857821

Summaries for Leber Congenital Amaurosis 10

OMIM : 56 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 inherited retinal disorder and leber congenital amaurosis. An important gene associated with Leber Congenital Amaurosis 10 is CEP290 (Centrosomal Protein 290), and among its related pathways/superpathways are Metabolism of fat-soluble vitamins and Phototransduction. 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 : 73 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

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 Leber Congenital Amaurosis 19

Diseases related to Leber Congenital Amaurosis 10 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 98)
# Related Disease Score Top Affiliating Genes
1 inherited retinal disorder 28.8 RPGR RPE65 RDH12 LCA5 IQCB1 GUCY2D
2 leber congenital amaurosis 24.8 TULP1 SPATA7 RPGRIP1 RPGR RPE65 RDH12
3 fundus dystrophy 24.7 TULP1 SPATA7 RPGRIP1 RPGR RPE65 RDH12
4 retinal aplasia 10.4 IQCB1 CEP290
5 nephronophthisis 11 10.4 IQCB1 CEP290
6 enophthalmos 10.4 GUCY2D CEP290
7 nephronophthisis 16 10.4 IQCB1 CEP290
8 cone-rod dystrophy 12 10.4 GUCY2D AIPL1
9 nephronophthisis 12 10.4 IQCB1 CEP290
10 nephronophthisis 7 10.3 IQCB1 CEP290
11 nephronophthisis 14 10.3 IQCB1 CEP290
12 nephronophthisis 19 10.3 RPGR CEP290
13 chorioretinal scar 10.3 RDH12 CRB1
14 renal-hepatic-pancreatic dysplasia 10.2 IQCB1 CEP290
15 red-green color blindness 10.2 RPGR RPE65
16 leber congenital amaurosis / early-onset severe retinal dystrophy 10.2 RPE65 CEP290 AIPL1
17 retinitis pigmentosa 35 10.2 RPGR RDH12
18 nephronophthisis 9 10.2 IQCB1 CEP290
19 cone-rod dystrophy 8 10.2 LCA5 GUCY2D AIPL1
20 bestrophinopathy, autosomal recessive 10.2 RPE65 CRB1
21 joubert syndrome 7 10.2 RPGRIP1 CEP290
22 retinitis pigmentosa 20 10.2 RPGR RPE65
23 retinitis pigmentosa 28 10.2 LCA5 CRX
24 severe early-childhood-onset retinal dystrophy 10.1 SPATA7 RPE65 LCA5
25 retinitis pigmentosa 34 10.1 RPGR CRX
26 cranioectodermal dysplasia 1 10.1 RPGR IQCB1 CEP290
27 achromatopsia 3 10.1 RPGRIP1 GUCY2D
28 night blindness 10.1 RPGR RPE65 GUCY2D
29 cone-rod dystrophy 1 10.1 RPGRIP1 RPGR
30 cone-rod dystrophy 3 10.1 GUCY2D CRX
31 scotoma 10.1 RPGR RPE65 GUCY2D
32 laurence-moon syndrome 10.1 RPGRIP1 RPGR
33 simpson-golabi-behmel syndrome, type 2 10.1 RPGRIP1 LCA5 CEP290
34 peripheral retinal degeneration 10.0 RPGR IMPDH1
35 joubert syndrome 22 10.0 IMPDH1 CRX
36 cone dystrophy 10.0 RPGR RPE65 GUCY2D
37 retinitis pigmentosa 1 10.0 IMPDH1 CRX
38 gyrate atrophy of choroid and retina 10.0 RPGR RPE65
39 retinitis pigmentosa 14 10.0 TULP1 RPGR
40 degeneration of macula and posterior pole 9.9 RPE65 CRX CRB1
41 retinitis pigmentosa 10 9.9 RPGR IMPDH1
42 alstrom syndrome 9.9 RPGR CEP290
43 retinitis pigmentosa 3 9.9 RPGRIP1 RPGR IQCB1
44 choroid disease 9.9 RPGR RPE65 GUCY2D CEP290
45 color blindness 9.9 RPGR RPE65 GUCY2D AIPL1
46 cone-rod dystrophy 13 9.9 SPATA7 RPGRIP1 RPGR
47 joubert syndrome 3 9.8 IQCB1 CNTLN CEP290
48 coloboma of macula 9.8 IQCB1 CRX CRB1 CEP290
49 retinitis pigmentosa 7 9.7 TULP1 RPGR
50 leber congenital amaurosis 16 9.7 SPATA7 LCA5 GUCY2D CRB1 AIPL1

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:

31
# Description HPO Frequency HPO Source Accession
1 seizures 31 very rare (1%) HP:0001250
2 visual impairment 31 HP:0000505
3 hyposmia 31 HP:0004409

Clinical features from OMIM:

611755

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 10:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.93 AIPL1 CEP290 CRB1 CRX GUCY2D LCA5
2 pigmentation MP:0001186 9.5 CEP290 CRB1 CRX LCA5 RPE65 RPGR
3 vision/eye MP:0005391 9.44 AIPL1 CEP290 CRB1 CRX GUCY2D IMPDH1

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 Approved, Nutraceutical Phase 2, Phase 3 52-90-4 5862

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:

40
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. 56 6
17554762 2007
2
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. 56 6
16909394 2006
3
Leber Congenital Amaurosis 61 6
20301475 2004
4
Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview 6
30285347 2018
5
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. 6
23105016 2013
6
Genetics and molecular basis of human peroxisome biogenesis disorders. 6
22871920 2012
7
Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations. 56
20805370 2010
8
Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons. 56
17898177 2007
9
Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. 6
17564974 2007
10
CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. 6
17564967 2007
11
Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. 6
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. 56
16632484 2006
13
Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype. 6
10384394 1999
14
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. 6
9398847 1997
15
Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. 6
9398848 1997
16
Gene editing shows promise in LCA10. 61
30718824 2019
17
Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. 61
30664785 2019
18
Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models. 61
30114557 2018
19
Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA. 61
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. 61
29771326 2018
21
Meta-analysis of GWAS on both Chinese and European populations identifies GPR173 as a novel X chromosome susceptibility gene for SLE. 61
29724251 2018
22
CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10. 61
28109959 2017
23
Mouse Models as Tools to Identify Genetic Pathways for Retinal Degeneration, as Exemplified by Leber's Congenital Amaurosis. 61
27150101 2016

Variations for Leber Congenital Amaurosis 10

ClinVar genetic disease variations for Leber Congenital Amaurosis 10:

6 (show all 31) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CEP290 NM_025114.3(CEP290):c.5344C>T (p.Arg1782Ter)SNV Pathogenic 217636 rs575767207 12:88472889-88472889 12:88079112-88079112
2 CEP290 NM_025114.3(CEP290):c.4882C>T (p.Gln1628Ter)SNV Pathogenic 217635 rs376493409 12:88476938-88476938 12:88083161-88083161
3 CEP290 NM_025114.3(CEP290):c.4393C>T (p.Arg1465Ter)SNV Pathogenic 217626 rs539400286 12:88479860-88479860 12:88086083-88086083
4 CEP290 NM_025114.3(CEP290):c.5668G>T (p.Gly1890Ter)SNV Pathogenic 1333 rs137852832 12:88471040-88471040 12:88077263-88077263
5 CEP290 NM_025114.3(CEP290):c.2991+1655A>GSNV Pathogenic 1337 rs281865192 12:88494960-88494960 12:88101183-88101183
6 CEP290 NM_025114.3(CEP290):c.2249T>G (p.Leu750Ter)SNV Pathogenic 1338 rs137852833 12:88505097-88505097 12:88111320-88111320
7 CEP290 NM_025114.3(CEP290):c.4723A>T (p.Lys1575Ter)SNV Pathogenic 1339 rs137852834 12:88477713-88477713 12:88083936-88083936
8 CEP290 CEP290, 4-BP DEL, 384TAGAdeletion Pathogenic 1340
9 CEP290 CEP290, 5-BP DEL, 1260TAAAGdeletion Pathogenic 1343
10 CEP290 NM_025114.3(CEP290):c.1711+1G>ASNV Pathogenic 156377 rs587783009 12:88512259-88512259 12:88118482-88118482
11 CEP290 NM_025114.3(CEP290):c.2248_2249delTT (p.Leu750Thrfs)deletion Pathogenic 156378 rs587783010 12:88505097-88505098 12:88111320-88111321
12 CEP290 NM_025114.3(CEP290):c.3904C>T (p.Gln1302Ter)SNV Pathogenic 156385 rs587783016 12:88482934-88482934 12:88089157-88089157
13 CEP290 NM_025114.3(CEP290):c.6869dupA (p.Asn2290Lysfs)duplication Pathogenic 156386 rs587783017 12:88449443-88449444 12:88055666-88055667
14 CEP290 NM_025114.3(CEP290):c.1066-1G>ASNV Pathogenic 439474 rs965522059 12:88519147-88519147 12:88125370-88125370
15 CEP290 NM_025114.3(CEP290):c.1078C>T (p.Arg360Ter)SNV Pathogenic 530911 rs776645403 12:88519134-88519134 12:88125357-88125357
16 CEP290 NM_025114.3(CEP290):c.4960C>T (p.Gln1654Ter)SNV Pathogenic 560436 rs1226324483 12:88476860-88476860 12:88083083-88083083
17 CEP290 NM_025114.3(CEP290):c.1429C>T (p.Arg477Ter)SNV Pathogenic/Likely pathogenic 523768 rs1170451277 12:88513984-88513984 12:88120207-88120207
18 CEP290 NM_025114.3(CEP290):c.4243G>T (p.Glu1415Ter)SNV Likely pathogenic 212730 rs797044604 12:88480227-88480227 12:88086450-88086450
19 CEP290 NM_025114.4(CEP290):c.732_733AG[1] (p.Glu245fs)short repeat Likely pathogenic 804466 12:88523588-88523589 12:88129811-88129812
20 CEP290 NM_025114.3(CEP290):c.4437+1G>ASNV Conflicting interpretations of pathogenicity 285948 rs760915898 12:88479815-88479815 12:88086038-88086038
21 CEP290 NM_025114.3(CEP290):c.6787A>G (p.Ser2263Gly)SNV Conflicting interpretations of pathogenicity 143156 rs77778467 12:88452656-88452656 12:88058879-88058879
22 CEP290 NM_025114.3(CEP290):c.4938A>G (p.Lys1646=)SNV Uncertain significance 241585 rs371582975 12:88476882-88476882 12:88083105-88083105
23 CEP290 NM_025114.3(CEP290):c.2551G>A (p.Val851Ile)SNV Uncertain significance 241583 rs764963626 12:88500808-88500808 12:88107031-88107031
24 CEP290 NM_025114.3(CEP290):c.5998A>G (p.Ile2000Val)SNV Uncertain significance 281249 rs183071230 12:88465084-88465084 12:88071307-88071307
25 CEP290 NM_025114.3(CEP290):c.963T>A (p.Asp321Glu)SNV Uncertain significance 286797 rs774072453 12:88520195-88520195 12:88126418-88126418
26 CEP290 NM_025114.3(CEP290):c.6629G>A (p.Arg2210His)SNV Uncertain significance 377291 rs371833544 12:88453691-88453691 12:88059914-88059914
27 CEP290 NM_025114.3(CEP290):c.1670G>A (p.Arg557His)SNV Uncertain significance 418122 rs184018899 12:88512301-88512301 12:88118524-88118524
28 CEP290 NM_025114.3(CEP290):c.4250A>G (p.Gln1417Arg)SNV Uncertain significance 166835 rs201504946 12:88480220-88480220 12:88086443-88086443
29 CEP290 NM_025114.3(CEP290):c.3660G>T (p.Lys1220Asn)SNV Uncertain significance 196713 rs201982308 12:88483178-88483178 12:88089401-88089401
30 CEP290 NM_025114.3(CEP290):c.5284C>T (p.Arg1762Cys)SNV Uncertain significance 197084 rs373307908 12:88472949-88472949 12:88079172-88079172
31 CEP290 NM_025114.3(CEP290):c.6392A>G (p.Glu2131Gly)SNV Uncertain significance 461788 rs184323010 12:88454737-88454737 12:88060960-88060960

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:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.91 SPATA7 RPGR LCA5 IQCB1 CNTLN CEP290
2 cell projection GO:0042995 9.85 TULP1 SPATA7 RPGRIP1 RPGR LCA5 CEP290
3 centrosome GO:0005813 9.8 RPGR IQCB1 CNTLN CEP290
4 microtubule organizing center GO:0005815 9.78 RPGR LCA5 IQCB1 CEP290
5 cilium GO:0005929 9.72 TULP1 RPGRIP1 RPGR LCA5 CEP290
6 centriole GO:0005814 9.63 IQCB1 CNTLN CEP290
7 axoneme GO:0005930 9.58 SPATA7 RPGRIP1 LCA5
8 ciliary basal body GO:0036064 9.56 SPATA7 RPGR LCA5 CEP290
9 photoreceptor inner segment GO:0001917 9.46 TULP1 RDH12 CRB1 AIPL1
10 photoreceptor outer segment GO:0001750 9.35 TULP1 SPATA7 RPGR IQCB1 GUCY2D
11 photoreceptor connecting cilium GO:0032391 9.02 SPATA7 RPGRIP1 LCA5 IQCB1 CEP290

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cilium assembly GO:0060271 9.69 RPGR IQCB1 CEP290
2 cell projection organization GO:0030030 9.67 RPGR IQCB1 CEP290
3 response to stimulus GO:0050896 9.61 TULP1 SPATA7 RPGRIP1 RPGR RPE65 RDH12
4 retina development in camera-type eye GO:0060041 9.58 TULP1 RPGRIP1 RPE65
5 eye photoreceptor cell development GO:0042462 9.56 TULP1 RPGRIP1 CRB1 CEP290
6 photoreceptor cell maintenance GO:0045494 9.55 TULP1 SPATA7 RDH12 LCA5 IQCB1
7 retina homeostasis GO:0001895 9.5 TULP1 RPE65 AIPL1
8 intraciliary transport GO:0042073 9.48 RPGR LCA5
9 regulation of rhodopsin mediated signaling pathway GO:0022400 9.46 GUCY2D AIPL1
10 detection of light stimulus involved in visual perception GO:0050908 9.43 TULP1 RPE65
11 protein localization to photoreceptor outer segment GO:1903546 9.37 TULP1 SPATA7
12 visual perception GO:0007601 9.28 TULP1 SPATA7 RPGRIP1 RPGR RPE65 RDH12

Sources for Leber Congenital Amaurosis 10

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17 EFO
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68 SNOMED-CT via HPO
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