LCA1
MCID: LBR004
MIFTS: 46

Leber Congenital Amaurosis 1 (LCA1)

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

Aliases & Classifications for Leber Congenital Amaurosis 1

MalaCards integrated aliases for Leber Congenital Amaurosis 1:

Name: Leber Congenital Amaurosis 1 58 12 54 76 30 13 6 15
Lca1 58 12 54 76
Amaurosis Congenita of Leber, Type 1 77 54 74
Amaurosis Congenita of Leber I 58 12
Retinal Blindness, Congenital 58 54
Crb 58 54
Retinal Blindness, Congenital; Crb 58
Leber Congenital Amaurosis, Type 1 41
Leber Congenital Amaurosis Type 1 54
Leber Congenital Amaurosis Type I 76
Lca 58

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
leber congenital amaurosis 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leber Congenital Amaurosis 1

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). (204000)

MalaCards based summary : Leber Congenital Amaurosis 1, also known as lca1, is related to leber congenital amaurosis 9 and retinal degeneration, and has symptoms including photophobia An important gene associated with Leber Congenital Amaurosis 1 is GUCY2D (Guanylate Cyclase 2D, Retinal), and among its related pathways/superpathways are Metabolism of fat-soluble vitamins and Phototransduction. Affiliated tissues include eye, retina and brain, and related phenotypes are nystagmus and intellectual disability

Disease Ontology : 12 A Leber congenital amaurosis characterized by severe cone-rod dystrophy with photophobia, high hyperopia, and poor but stable vision with no visual improvement and that has material basis in mutation in the GUCY2D gene on chromosome 17p13.

UniProtKB/Swiss-Prot : 76 Leber congenital amaurosis 1: 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 1

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 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 57)
# Related Disease Score Top Affiliating Genes
1 leber congenital amaurosis 9 31.6 GUCY2D TULP1
2 retinal degeneration 29.2 GUCA1A GUCY2D RD3 TULP1
3 leber congenital amaurosis 28.2 TULP1 RD3 GUCY2D GUCA1B GUCA1A GRK1
4 retinitis pigmentosa 27.5 ARR3 GRK1 GUCA1A GUCA1B GUCY2D RD3
5 littoral cell angioma of the spleen 11.8
6 anomalous left coronary artery from the pulmonary artery 11.3
7 senior-loken syndrome 1 11.2
8 leber congenital amaurosis 2 11.1
9 joubert syndrome with oculorenal anomalies 11.1
10 leber congenital amaurosis / early-onset severe retinal dystrophy 11.1
11 congenital muscular dystrophy with cerebellar involvement 11.1
12 nystagmus 1, congenital, x-linked 11.1
13 leber congenital amaurosis 3 11.1
14 leber congenital amaurosis 4 11.1
15 leber congenital amaurosis 10 11.1
16 leber congenital amaurosis 14 11.1
17 leber congenital amaurosis 15 11.1
18 senior-loken syndrome 5 11.0
19 leber congenital amaurosis 6 11.0
20 leber congenital amaurosis 7 11.0
21 leber congenital amaurosis 8 11.0
22 leber congenital amaurosis 11 11.0
23 leber congenital amaurosis 5 10.2
24 cholera 10.1
25 pneumonia 10.1
26 leukoencephalopathy, brain calcifications, and cysts 10.1
27 leukoencephalopathy, cerebral calcifications, and cysts 10.1
28 eye degenerative disease 10.0 GUCA1A GUCY2D
29 leber congenital amaurosis 12 10.0 GUCY2D RD3
30 prolonged electroretinal response suppression 9.9 GRK1 GUCY2D
31 coloboma of macula 9.9
32 multiple sclerosis 9.9
33 systemic lupus erythematosus 9.9
34 pelger-huet anomaly 9.9
35 rheumatoid arthritis 9.9
36 cystic fibrosis 9.9
37 pulmonary alveolar microlithiasis 9.9
38 cardiomyopathy, infantile hypertrophic 9.9
39 liver cirrhosis 9.9
40 obstructive nephropathy 9.9
41 alcoholic cardiomyopathy 9.9
42 cholestasis 9.9
43 rectum cancer 9.9
44 kidney cancer 9.9
45 myocarditis 9.9
46 lupus erythematosus 9.9
47 heparin-induced thrombocytopenia 9.9
48 polymyositis 9.9
49 streptococcal group a invasive disease 9.9
50 achromatopsia 3 9.9 GUCY2D TULP1

Graphical network of the top 20 diseases related to Leber Congenital Amaurosis 1:



Diseases related to Leber Congenital Amaurosis 1

Symptoms & Phenotypes for Leber Congenital Amaurosis 1

Human phenotypes related to Leber Congenital Amaurosis 1:

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 nystagmus 33 HP:0000639
2 intellectual disability 33 HP:0001249
3 cataract 33 HP:0000518
4 hepatomegaly 33 HP:0002240
5 sensorineural hearing impairment 33 HP:0000407
6 blindness 33 HP:0000618
7 photophobia 33 HP:0000613
8 growth delay 33 HP:0001510
9 keratoconus 33 HP:0000563
10 pigmentary retinopathy 33 HP:0000580
11 fundus atrophy 33 HP:0001099
12 eye poking 33 HP:0001483
13 hyperthreoninemia 33 HP:0003354
14 hyperthreoninuria 33 HP:0003296
15 decreased light- and dark-adapted electroretinogram amplitude 33 HP:0000654

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
cataract
blindness
photophobia
keratoconus
more
Neurologic Central Nervous System:
mental retardation

Head And Neck Ears:
sensory hearing loss

Abdomen Liver:
hepatomegaly

Growth Other:
retarded growth

Laboratory Abnormalities:
hyperthreoninemia
hyperthreoninuria

Clinical features from OMIM:

204000

UMLS symptoms related to Leber Congenital Amaurosis 1:


photophobia

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 1:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.43 GRK1 GUCA1A GUCY2D RD3 RP1 TULP1
2 vision/eye MP:0005391 9.23 ARR3 GRK1 GUCA1A GUCA1B GUCY2D RD3

Drugs & Therapeutics for Leber Congenital Amaurosis 1

Search Clinical Trials , NIH Clinical Center for Leber Congenital Amaurosis 1

Genetic Tests for Leber Congenital Amaurosis 1

Genetic tests related to Leber Congenital Amaurosis 1:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 1 30 GUCY2D

Anatomical Context for Leber Congenital Amaurosis 1

MalaCards organs/tissues related to Leber Congenital Amaurosis 1:

42
Eye, Retina, Brain, Kidney, Liver, Spleen

Publications for Leber Congenital Amaurosis 1

Articles related to Leber Congenital Amaurosis 1:

(show all 12)
# Title Authors Year
1
A Mini-review: Animal Models of GUCY2D Leber Congenital Amaurosis (LCA1). ( 26427419 )
2016
2
Impaired association of retinal degeneration-3 with guanylate cyclase-1 and guanylate cyclase-activating protein-1 leads to leber congenital amaurosis-1. ( 25477517 )
2015
3
Gene Therapy Fully Restores Vision to the All-Cone Nrl(-/-) Gucy2e(-/-) Mouse Model of Leber Congenital Amaurosis-1. ( 26247368 )
2015
4
Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1. ( 21647387 )
2011
5
A tomato ER-type Ca2+-ATPase, LCA1, has a low thapsigargin-sensitivity and can transport manganese. ( 19056336 )
2009
6
The yeast acylglycerol acyltransferase LCA1 is a key component of Lands cycle for phosphatidylcholine turnover. ( 17996202 )
2007
7
Prenatal human ocular degeneration occurs in Leber's Congenital Amaurosis (LCA1 and 2). ( 15180248 )
2003
8
Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin. ( 12325031 )
2002
9
Alternative transcription initiation sites generate two LCA1 Ca2+-ATPase mRNA transcripts in tomato roots. ( 10394952 )
1999
10
Functional consequences of a rod outer segment membrane guanylate cyclase (ROS-GC1) gene mutation linked with Leber's congenital amaurosis. ( 9888789 )
1999
11
A retGC-1 mutation in autosomal dominant cone-rod dystrophy. ( 9683616 )
1998
12
Evidence of genetic heterogeneity of Leber's congenital amaurosis (LCA) and mapping of LCA1 to chromosome 17p13. ( 8641699 )
1996

Variations for Leber Congenital Amaurosis 1

UniProtKB/Swiss-Prot genetic disease variations for Leber Congenital Amaurosis 1:

76 (show all 19)
# Symbol AA change Variation ID SNP ID
1 GUCY2D p.Ala362Ser VAR_009129 rs61749677
2 GUCY2D p.Ile573Val VAR_009130 rs61749756
3 GUCY2D p.Phe565Ser VAR_009131 rs61749755
4 GUCY2D p.Pro858Ser VAR_009134 rs61750176
5 GUCY2D p.Leu954Pro VAR_009135 rs61750182
6 GUCY2D p.Cys105Tyr VAR_023770 rs61749669
7 GUCY2D p.Leu325Pro VAR_023771 rs61749675
8 GUCY2D p.Thr55Met VAR_067169 rs201414567
9 GUCY2D p.Glu103Val VAR_067170
10 GUCY2D p.Thr312Met VAR_067171 rs61749673
11 GUCY2D p.Arg438Cys VAR_067174 rs565948960
12 GUCY2D p.Trp640Leu VAR_067175
13 GUCY2D p.Arg660Gln VAR_067176 rs61750162
14 GUCY2D p.Asp728His VAR_067177
15 GUCY2D p.Ile734Ala VAR_067178
16 GUCY2D p.Arg768Trp VAR_067179 rs61750168
17 GUCY2D p.Met784Arg VAR_067180 rs375010731
18 GUCY2D p.Arg795Gln VAR_067181 rs61750171
19 GUCY2D p.Ser1007Leu VAR_067182

ClinVar genetic disease variations for Leber Congenital Amaurosis 1:

6 (show top 50) (show all 55)
# Gene Variation Type Significance SNP ID Assembly Location
1 GUCY2D NM_000180.3(GUCY2D): c.1694T> C (p.Phe565Ser) single nucleotide variant Pathogenic rs61749755 GRCh37 Chromosome 17, 7912849: 7912849
2 GUCY2D NM_000180.3(GUCY2D): c.1694T> C (p.Phe565Ser) single nucleotide variant Pathogenic rs61749755 GRCh38 Chromosome 17, 8009531: 8009531
3 GUCY2D GUCY2D, 1-BP DEL, 460C deletion Pathogenic
4 GUCY2D GUCY2D, 1-BP DEL, 693C deletion Pathogenic
5 GUCY2D NM_000180.3(GUCY2D): c.154G> T (p.Ala52Ser) single nucleotide variant Benign rs61749665 GRCh37 Chromosome 17, 7906519: 7906519
6 GUCY2D NM_000180.3(GUCY2D): c.154G> T (p.Ala52Ser) single nucleotide variant Benign rs61749665 GRCh38 Chromosome 17, 8003201: 8003201
7 GUCY2D GUCY2D, 1-BP DEL, 2943G deletion Pathogenic
8 GUCY2D NM_000180.3(GUCY2D): c.3233_3236dupACCA (p.His1079Glnfs) duplication Pathogenic rs386834239 GRCh37 Chromosome 17, 7919769: 7919772
9 GUCY2D NM_000180.3(GUCY2D): c.3233_3236dupACCA (p.His1079Glnfs) duplication Pathogenic rs386834239 GRCh38 Chromosome 17, 8016451: 8016454
10 GUCY2D NM_000180.3(GUCY2D): c.1956+2T> A single nucleotide variant Likely pathogenic rs61749758 GRCh37 Chromosome 17, 7915670: 7915670
11 GUCY2D NM_000180.3(GUCY2D): c.1956+2T> A single nucleotide variant Likely pathogenic rs61749758 GRCh38 Chromosome 17, 8012352: 8012352
12 GUCY2D NM_000180.3(GUCY2D): c.2302C> T (p.Arg768Trp) single nucleotide variant Pathogenic rs61750168 GRCh37 Chromosome 17, 7917236: 7917236
13 GUCY2D NM_000180.3(GUCY2D): c.2302C> T (p.Arg768Trp) single nucleotide variant Pathogenic rs61750168 GRCh38 Chromosome 17, 8013918: 8013918
14 GUCY2D NM_000180.3(GUCY2D): c.2927G> T (p.Arg976Leu) single nucleotide variant Uncertain significance rs61750184 GRCh37 Chromosome 17, 7918803: 7918803
15 GUCY2D NM_000180.3(GUCY2D): c.2927G> T (p.Arg976Leu) single nucleotide variant Uncertain significance rs61750184 GRCh38 Chromosome 17, 8015485: 8015485
16 GUCY2D NM_000180.3(GUCY2D): c.389del (p.Pro130Leufs) deletion Pathogenic rs61749670 GRCh37 Chromosome 17, 7906754: 7906754
17 GUCY2D NM_000180.3(GUCY2D): c.389del (p.Pro130Leufs) deletion Pathogenic rs61749670 GRCh38 Chromosome 17, 8003436: 8003436
18 GUCY2D NM_000180.3(GUCY2D): c.2577G> T (p.Pro859=) single nucleotide variant Benign rs112372281 GRCh37 Chromosome 17, 7918177: 7918177
19 GUCY2D NM_000180.3(GUCY2D): c.2577G> T (p.Pro859=) single nucleotide variant Benign rs112372281 GRCh38 Chromosome 17, 8014859: 8014859
20 GUCY2D NM_000180.3(GUCY2D): c.3225-7C> T single nucleotide variant Benign rs79887212 GRCh37 Chromosome 17, 7919754: 7919754
21 GUCY2D NM_000180.3(GUCY2D): c.3225-7C> T single nucleotide variant Benign rs79887212 GRCh38 Chromosome 17, 8016436: 8016436
22 GUCY2D NM_000180.3(GUCY2D): c.3297G> A (p.Pro1099=) single nucleotide variant Benign rs142351773 GRCh37 Chromosome 17, 7919833: 7919833
23 GUCY2D NM_000180.3(GUCY2D): c.3297G> A (p.Pro1099=) single nucleotide variant Benign rs142351773 GRCh38 Chromosome 17, 8016515: 8016515
24 GUCY2D NM_000180.3(GUCY2D): c.3044-7G> T single nucleotide variant Benign rs56348143 GRCh38 Chromosome 17, 8015920: 8015920
25 GUCY2D NM_000180.3(GUCY2D): c.3044-7G> T single nucleotide variant Benign rs56348143 GRCh37 Chromosome 17, 7919238: 7919238
26 GUCY2D NG_009092.1: g.15407_15601del195 deletion Pathogenic rs1555635550 GRCh37 Chromosome 17, 7916394: 7916588
27 GUCY2D NG_009092.1: g.15407_15601del195 deletion Pathogenic rs1555635550 GRCh38 Chromosome 17, 8013076: 8013270
28 GUCY2D NM_000180.3(GUCY2D): c.1040_1041delTT (p.Phe347Trpfs) deletion Likely pathogenic rs763890649 GRCh38 Chromosome 17, 8006376: 8006377
29 GUCY2D NM_000180.3(GUCY2D): c.1040_1041delTT (p.Phe347Trpfs) deletion Likely pathogenic rs763890649 GRCh37 Chromosome 17, 7909694: 7909695
30 GUCY2D NM_000180.3(GUCY2D): c.2377delG (p.Glu793Asnfs) deletion Pathogenic rs1555635668 GRCh38 Chromosome 17, 8013993: 8013993
31 GUCY2D NM_000180.3(GUCY2D): c.2377delG (p.Glu793Asnfs) deletion Pathogenic rs1555635668 GRCh37 Chromosome 17, 7917311: 7917311
32 GUCY2D NM_000180.3(GUCY2D): c.696G> T (p.Lys232Asn) single nucleotide variant Uncertain significance rs181800610 GRCh37 Chromosome 17, 7907061: 7907061
33 GUCY2D NM_000180.3(GUCY2D): c.696G> T (p.Lys232Asn) single nucleotide variant Uncertain significance rs181800610 GRCh38 Chromosome 17, 8003743: 8003743
34 GUCY2D NM_000180.3(GUCY2D): c.2598G> C (p.Lys866Asn) single nucleotide variant Uncertain significance rs201587670 GRCh38 Chromosome 17, 8014880: 8014880
35 GUCY2D NM_000180.3(GUCY2D): c.2598G> C (p.Lys866Asn) single nucleotide variant Uncertain significance rs201587670 GRCh37 Chromosome 17, 7918198: 7918198
36 GUCY2D NM_000180.3(GUCY2D): c.1119G> A (p.Val373=) single nucleotide variant Benign rs56034424 GRCh37 Chromosome 17, 7909773: 7909773
37 GUCY2D NM_000180.3(GUCY2D): c.1119G> A (p.Val373=) single nucleotide variant Benign rs56034424 GRCh38 Chromosome 17, 8006455: 8006455
38 GUCY2D NM_000180.3(GUCY2D): c.2563C> T (p.Gln855Ter) single nucleotide variant Pathogenic rs1555635778 GRCh37 Chromosome 17, 7918069: 7918069
39 GUCY2D NM_000180.3(GUCY2D): c.2563C> T (p.Gln855Ter) single nucleotide variant Pathogenic rs1555635778 GRCh38 Chromosome 17, 8014751: 8014751
40 TULP1 NM_003322.5(TULP1): c.524dup (p.Pro176Thrfs) duplication Pathogenic rs1327062642 GRCh37 Chromosome 6, 35477681: 35477681
41 TULP1 NM_003322.5(TULP1): c.524dup (p.Pro176Thrfs) duplication Pathogenic rs1327062642 GRCh38 Chromosome 6, 35509904: 35509904
42 RP1 NM_006269.1(RP1): c.1267_1656del390insA (p.Ala423Asnfs) indel Uncertain significance rs1554519422 GRCh37 Chromosome 8, 55537709: 55538098
43 RP1 NM_006269.1(RP1): c.1267_1656del390insA (p.Ala423Asnfs) indel Uncertain significance rs1554519422 GRCh38 Chromosome 8, 54625149: 54625538
44 GUCY2D NM_000180.3(GUCY2D): c.2303G> A (p.Arg768Gln) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 8013919: 8013919
45 GUCY2D NM_000180.3(GUCY2D): c.2303G> A (p.Arg768Gln) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 7917237: 7917237
46 GUCY2D NM_000180.3(GUCY2D): c.2618C> G (p.Pro873Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 7918218: 7918218
47 GUCY2D NM_000180.3(GUCY2D): c.2618C> G (p.Pro873Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 8014900: 8014900
48 GUCY2D NM_000180.3(GUCY2D): c.3224+1G> C single nucleotide variant Pathogenic GRCh38 Chromosome 17, 8016291: 8016291
49 GUCY2D NM_000180.3(GUCY2D): c.3224+1G> C single nucleotide variant Pathogenic GRCh37 Chromosome 17, 7919609: 7919609
50 GUCY2D NC_000017.11: g.(?_8002902)_(8016550_?)del deletion Pathogenic GRCh38 Chromosome 17, 8002902: 8016550

Expression for Leber Congenital Amaurosis 1

Search GEO for disease gene expression data for Leber Congenital Amaurosis 1.

Pathways for Leber Congenital Amaurosis 1

GO Terms for Leber Congenital Amaurosis 1

Cellular components related to Leber Congenital Amaurosis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 photoreceptor outer segment GO:0001750 9.33 ARR3 RP1 TULP1
2 photoreceptor disc membrane GO:0097381 9.26 GRK1 GUCA1A GUCA1B GUCY2D
3 photoreceptor inner segment GO:0001917 9.02 ARR3 GUCA1A GUCA1B RP1 TULP1

Biological processes related to Leber Congenital Amaurosis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to stimulus GO:0050896 9.56 ARR3 GRK1 GUCA1A GUCA1B GUCY2D RD3
2 retina development in camera-type eye GO:0060041 9.5 RD3 RP1 TULP1
3 photoreceptor cell maintenance GO:0045494 9.46 RP1 TULP1
4 regulation of rhodopsin mediated signaling pathway GO:0022400 9.46 GRK1 GUCA1A GUCA1B GUCY2D
5 phototransduction GO:0007602 9.43 GUCA1A GUCA1B
6 receptor guanylyl cyclase signaling pathway GO:0007168 9.4 GUCA1B GUCY2D
7 positive regulation of guanylate cyclase activity GO:0031284 9.37 GUCA1A GUCA1B
8 regulation of guanylate cyclase activity GO:0031282 9.26 GUCA1A GUCA1B
9 visual perception GO:0007601 9.23 ARR3 GRK1 GUCA1A GUCA1B GUCY2D RD3

Molecular functions related to Leber Congenital Amaurosis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium sensitive guanylate cyclase activator activity GO:0008048 8.96 GUCA1A GUCA1B
2 guanylate cyclase regulator activity GO:0030249 8.62 GUCA1A GUCA1B

Sources for Leber Congenital Amaurosis 1

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