LCA9
MCID: LBR019
MIFTS: 43

Leber Congenital Amaurosis 9 (LCA9)

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

Aliases & Classifications for Leber Congenital Amaurosis 9

MalaCards integrated aliases for Leber Congenital Amaurosis 9:

Name: Leber Congenital Amaurosis 9 56 12 52 73 29 13 6 15 71
Lca9 56 12 52 73
Amaurosis Congenita of Leber, Type 9 52
Leber Congenital Amaurosis, Type 9 39
Leber Congenital Amaurosis Type 9 52

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
visual impairment is present at birth and is progressive


HPO:

31
leber congenital amaurosis 9:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110005
OMIM 56 608553
OMIM Phenotypic Series 56 PS204000
MeSH 43 D057130
ICD10 32 H35.5
MedGen 41 C1837873
UMLS 71 C1837873

Summaries for Leber Congenital Amaurosis 9

OMIM : 56 Early-onset neurodegeneration in the human retina can lead to Leber congenital amaurosis (LCA), the most severe human form of inherited photoreceptor-neuron degeneration resulting in congenital blindness, with an incidence of approximately 1 in 80,000 (summary by Koenekoop et al., 2012). NMNAT1 (608700) mutations consistently cause severe and rapidly progressive macular degeneration leading to severe central atrophy with an appearance of congenital macular coloboma in the neonatal period, as well as an unusual early-onset atrophy of the optic nerve (Perrault et al., 2012). (608553)

MalaCards based summary : Leber Congenital Amaurosis 9, also known as lca9, is related to yemenite deaf-blind hypopigmentation syndrome and retinal degeneration. An important gene associated with Leber Congenital Amaurosis 9 is NMNAT1 (Nicotinamide Nucleotide Adenylyltransferase 1), and among its related pathways/superpathways are Drug metabolism - cytochrome P450 and Metabolism of fat-soluble vitamins. Affiliated tissues include retina, eye and bone, and related phenotypes are nyctalopia and photophobia

Disease Ontology : 12 A Leber congenital amaurosis that has material basis in mutation in the NMNAT1 gene on chromosome 1p36.

UniProtKB/Swiss-Prot : 73 Leber congenital amaurosis 9: 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 9

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

(show top 50) (show all 68)
# Related Disease Score Top Affiliating Genes
1 yemenite deaf-blind hypopigmentation syndrome 29.1 RPE65 GUCY2D CRB1 CEP290 AIPL1
2 retinal degeneration 25.8 TULP1 SPATA7 RPE65 RDH12 NMNAT1 LRAT
3 leber congenital amaurosis 25.7 TULP1 SPATA7 RPE65 RDH12 NMNAT1 LRAT
4 3-methylglutaconic aciduria, type iii 10.2
5 optic disk drusen 10.2 TULP1 CRB1
6 chorioretinal scar 10.2 RDH12 CRB1
7 cone-rod dystrophy 12 10.1 GUCY2D AIPL1
8 retinal ciliopathy 10.0 SPATA7 CEP290
9 simpson-golabi-behmel syndrome, type 2 10.0 LCA5 CEP290
10 cone-rod dystrophy 8 10.0 LCA5 GUCY2D AIPL1
11 enophthalmos 9.9 GUCY2D CEP290
12 retinitis pigmentosa 28 9.9 LCA5 CRX
13 pseudoretinitis pigmentosa 9.9 TULP1 IMPDH1 CRB1
14 joubert syndrome 22 9.9 IMPDH1 CRX
15 microphthalmia, syndromic 9 9.8 RDH12 LRAT
16 cone-rod dystrophy 3 9.8 GUCY2D CRX
17 bestrophinopathy, autosomal recessive 9.7 RPE65 CRB1
18 color blindness 9.6 RPE65 GUCY2D AIPL1
19 scotoma 9.6 RPE65 GUCY2D
20 retinitis 9.5 RPE65 IMPDH1 CRB1
21 leber congenital amaurosis / early-onset severe retinal dystrophy 9.5 RPE65 CEP290 AIPL1
22 leber congenital amaurosis 16 9.5 SPATA7 LCA5 GUCY2D CRB1 AIPL1
23 night blindness 9.5 RPE65 LRAT GUCY2D
24 cone-rod dystrophy 6 9.5 RPE65 GUCY2D CRB1
25 retinitis pigmentosa 1 9.4 IMPDH1 CRX
26 choroid disease 9.4 RPE65 GUCY2D CEP290
27 usher syndrome, type i 9.4 RPE65 IMPDH1 CRX
28 coloboma of macula 9.4 NMNAT1 CRX CRB1 CEP290
29 degeneration of macula and posterior pole 9.3 RPE65 CRX CRB1
30 leber congenital amaurosis 13 9.3 TULP1 SPATA7 RDH12 LRAT LCA5 AIPL1
31 severe early-childhood-onset retinal dystrophy 9.3 SPATA7 RPE65 LRAT LCA5
32 enhanced s-cone syndrome 9.2 TULP1 RPE65 CRX AIPL1
33 usher syndrome type 2 9.2 TULP1 RPE65 CRB1 CEP290
34 retinoschisis 1, x-linked, juvenile 9.2 RPE65 CRX CRB1 AIPL1
35 leber congenital amaurosis 14 9.0 SPATA7 RDH12 NMNAT1 LRAT LCA5 IMPDH1
36 leber congenital amaurosis 11 9.0 SPATA7 RDH12 LCA5 IMPDH1 GUCY2D CRB1
37 leber congenital amaurosis 5 9.0 TULP1 SPATA7 RDH12 LRAT LCA5 IMPDH1
38 choroidal dystrophy, central areolar, 1 8.9 SPATA7 RPE65 GUCY2D CRX AIPL1
39 usher syndrome 8.9 TULP1 RPE65 RDH12 LCA5 CRB1 CEP290
40 pseudopapilledema 8.8 RPE65 RDH12 GUCY2D CRB1 CEP290 AIPL1
41 leber congenital amaurosis 15 8.8 TULP1 SPATA7 RDH12 NMNAT1 LRAT LCA5
42 leber congenital amaurosis 8 8.8 TULP1 SPATA7 RDH12 LCA5 IMPDH1 GUCY2D
43 hereditary retinal dystrophy 8.7 SPATA7 RPE65 RDH12 GUCY2D CRB1 CEP290
44 fundus albipunctatus 8.5 TULP1 RPE65 RDH12 LRAT CRX CRB1
45 leber congenital amaurosis 12 8.4 SPATA7 RPE65 RDH12 NMNAT1 LCA5 IMPDH1
46 inherited retinal disorder 8.3 RPE65 RDH12 LRAT LCA5 GUCY2D CRB1
47 usher syndrome, type iiia 8.3 TULP1 RPE65 RDH12 LRAT LCA5 IMPDH1
48 leber congenital amaurosis 7 8.3 TULP1 SPATA7 RDH12 LCA5 IMPDH1 GUCY2D
49 cone-rod dystrophy 2 8.0 TULP1 RPE65 NMNAT1 GUCY2D CRX CRB1
50 macular degeneration, age-related, 1 8.0 RPE65 RDH12 LRAT GUCY2D CRX CRB1

Graphical network of the top 20 diseases related to Leber Congenital Amaurosis 9:



Diseases related to Leber Congenital Amaurosis 9

Symptoms & Phenotypes for Leber Congenital Amaurosis 9

Human phenotypes related to Leber Congenital Amaurosis 9:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 nyctalopia 31 occasional (7.5%) HP:0000662
2 photophobia 31 occasional (7.5%) HP:0000613
3 nystagmus 31 HP:0000639
4 optic atrophy 31 HP:0000648
5 optic disc pallor 31 HP:0000543
6 hypermetropia 31 HP:0000540
7 macular coloboma 31 HP:0001116
8 attenuation of retinal blood vessels 31 HP:0007843

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
nystagmus
optic disc pallor
macular coloboma
attenuation of retinal blood vessels
hyperopia
more

Clinical features from OMIM:

608553

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 9:

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 NMNAT1 RPE65
3 vision/eye MP:0005391 9.44 AIPL1 CEP290 CRB1 CRX GUCY2D IMPDH1

Drugs & Therapeutics for Leber Congenital Amaurosis 9

Search Clinical Trials , NIH Clinical Center for Leber Congenital Amaurosis 9

Genetic Tests for Leber Congenital Amaurosis 9

Genetic tests related to Leber Congenital Amaurosis 9:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 9 29 NMNAT1

Anatomical Context for Leber Congenital Amaurosis 9

MalaCards organs/tissues related to Leber Congenital Amaurosis 9:

40
Retina, Eye, Bone

Publications for Leber Congenital Amaurosis 9

Articles related to Leber Congenital Amaurosis 9:

(show all 21)
# Title Authors PMID Year
1
NMNAT1 mutations cause Leber congenital amaurosis. 61 56 6
22842227 2012
2
Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. 61 56 6
22842230 2012
3
Identification of a locus (LCA9) for Leber's congenital amaurosis on chromosome 1p36. 61 56 6
12734549 2003
4
Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. 56 6
22842229 2012
5
Leber Congenital Amaurosis 61 6
20301475 2004
6
Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview 6
30285347 2018
7
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. 6
23105016 2013
8
Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. 6
22842231 2012
9
Genetics and molecular basis of human peroxisome biogenesis disorders. 6
22871920 2012
10
Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity. 56
17132048 2006
11
Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype. 6
10384394 1999
12
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. 6
9398847 1997
13
Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. 6
9398848 1997
14
Relative frequency of inherited retinal dystrophies in Brazil. 61
30374144 2018
15
NMNAT1 E257K variant, associated with Leber Congenital Amaurosis (LCA9), causes a mild retinal degeneration phenotype. 61
29674119 2018
16
Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype. 61
28369829 2018
17
Mouse Models of NMNAT1-Leber Congenital Amaurosis (LCA9) Recapitulate Key Features of the Human Disease. 61
27207593 2016
18
Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5'UTR Mutations and Copy-Number Variations of NMNAT1. 61
26316326 2015
19
Characterization of Leber Congenital Amaurosis-associated NMNAT1 Mutants. 61
26018082 2015
20
Genotype-phenotype correlation for leber congenital amaurosis in Northern Pakistan. 61
20065226 2010
21
Exclusion of LCA5 locus in a consanguineous Turkish family with macular coloboma-type LCA. 61
16082399 2006

Variations for Leber Congenital Amaurosis 9

ClinVar genetic disease variations for Leber Congenital Amaurosis 9:

6 (show all 13) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NMNAT1 NM_022787.4(NMNAT1):c.817A>G (p.Asn273Asp)SNV Pathogenic 37135 rs387907291 1:10042736-10042736 1:9982678-9982678
2 NMNAT1 NM_022787.4(NMNAT1):c.451G>T (p.Val151Phe)SNV Pathogenic 37136 rs387907292 1:10042370-10042370 1:9982312-9982312
3 NMNAT1 NM_022787.4(NMNAT1):c.710G>T (p.Arg237Leu)SNV Pathogenic 37138 rs368062092 1:10042629-10042629 1:9982571-9982571
4 NMNAT1 NM_022787.4(NMNAT1):c.457C>G (p.Leu153Val)SNV Pathogenic 37139 rs387907293 1:10042376-10042376 1:9982318-9982318
5 NMNAT1 NM_022787.4(NMNAT1):c.25G>A (p.Val9Met)SNV Pathogenic 37140 rs387907294 1:10032156-10032156 1:9972098-9972098
6 NMNAT1 NM_022787.4(NMNAT1):c.507G>A (p.Trp169Ter)SNV Pathogenic 265453 rs371526758 1:10042426-10042426 1:9982368-9982368
7 NMNAT1 NC_000001.10:g.(?_10041069)_(10042779_?)deldeletion Pathogenic 464669 1:10041069-10042779 1:9981011-9982721
8 NMNAT1 NM_022787.4(NMNAT1):c.716T>C (p.Leu239Ser)SNV Pathogenic 464670 rs778606847 1:10042635-10042635 1:9982577-9982577
9 NMNAT1 NM_022787.4(NMNAT1):c.838T>C (p.Ter280Gln)SNV Pathogenic 37132 rs387907290 1:10042757-10042757 1:9982699-9982699
10 NMNAT1 NM_022787.4(NMNAT1):c.619C>T (p.Arg207Trp)SNV Pathogenic 37133 rs142968179 1:10042538-10042538 1:9982480-9982480
11 NMNAT1 NM_022787.4(NMNAT1):c.769G>A (p.Glu257Lys)SNV Pathogenic/Likely pathogenic 37134 rs150726175 1:10042688-10042688 1:9982630-9982630
12 NMNAT1 NM_022787.4(NMNAT1):c.205A>T (p.Met69Leu)SNV Likely pathogenic 635553 1:10035739-10035739 1:9975681-9975681
13 NMNAT1 NM_022787.4(NMNAT1):c.115+3A>GSNV Benign/Likely benign 522303 rs181504239 1:10032249-10032249 1:9972191-9972191

UniProtKB/Swiss-Prot genetic disease variations for Leber Congenital Amaurosis 9:

73 (show all 28)
# Symbol AA change Variation ID SNP ID
1 NMNAT1 p.Val9Met VAR_068856 rs387907294
2 NMNAT1 p.Ala13Thr VAR_068857 rs138613460
3 NMNAT1 p.Ile20Asn VAR_068858 rs761948762
4 NMNAT1 p.Asp33Gly VAR_068859
5 NMNAT1 p.Met35Thr VAR_068860
6 NMNAT1 p.Ala54Val VAR_068861 rs760965874
7 NMNAT1 p.Arg66Trp VAR_068862 rs763325435
8 NMNAT1 p.Val67Phe VAR_068863 rs756903689
9 NMNAT1 p.Met69Val VAR_068864 rs372066126
10 NMNAT1 p.Leu72His VAR_068865
11 NMNAT1 p.Val98Gly VAR_068866 rs771336246
12 NMNAT1 p.Ala147Pro VAR_068867
13 NMNAT1 p.Val151Phe VAR_068868 rs387907292
14 NMNAT1 p.Leu153Pro VAR_068869
15 NMNAT1 p.Leu153Val VAR_068870 rs387907293
16 NMNAT1 p.Gly156Arg VAR_068871 rs124451164
17 NMNAT1 p.Asp173Gly VAR_068872
18 NMNAT1 p.Val178Met VAR_068873 rs757724544
19 NMNAT1 p.Tyr181Cys VAR_068874 rs748913297
20 NMNAT1 p.Ile184Met VAR_068875
21 NMNAT1 p.Arg207Trp VAR_068876 rs142968179
22 NMNAT1 p.Ile217Asn VAR_068877
23 NMNAT1 p.Arg237Cys VAR_068878 rs375110174
24 NMNAT1 p.Arg237Leu VAR_068879 rs368062092
25 NMNAT1 p.Leu239Ser VAR_068880 rs778606847
26 NMNAT1 p.His251Pro VAR_068881 rs120849529
27 NMNAT1 p.Glu257Lys VAR_068882 rs150726175
28 NMNAT1 p.Asn273Asp VAR_068883 rs387907291

Expression for Leber Congenital Amaurosis 9

Search GEO for disease gene expression data for Leber Congenital Amaurosis 9.

Pathways for Leber Congenital Amaurosis 9

Pathways related to Leber Congenital Amaurosis 9 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.4 RPE65 RDH12 LRAT IMPDH1
2
Show member pathways
11.95 RPE65 RDH12 LRAT GUCY2D
3
Show member pathways
11.45 RPE65 RDH12 LRAT GUCY2D
4
Show member pathways
11.17 RPE65 RDH12 LRAT
5 10.98 RPE65 RDH12 LRAT
6 10.9 RPE65 RDH12 LRAT GUCY2D

GO Terms for Leber Congenital Amaurosis 9

Cellular components related to Leber Congenital Amaurosis 9 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ciliary basal body GO:0036064 9.43 SPATA7 LCA5 CEP290
2 photoreceptor outer segment GO:0001750 9.33 TULP1 SPATA7 GUCY2D
3 photoreceptor connecting cilium GO:0032391 9.13 SPATA7 LCA5 CEP290
4 photoreceptor inner segment GO:0001917 8.92 TULP1 RDH12 CRB1 AIPL1

Biological processes related to Leber Congenital Amaurosis 9 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 retinoid metabolic process GO:0001523 9.61 RPE65 RDH12 LRAT
2 response to stimulus GO:0050896 9.56 TULP1 SPATA7 RPE65 RDH12 LRAT GUCY2D
3 retinol metabolic process GO:0042572 9.54 RPE65 RDH12 LRAT
4 retina homeostasis GO:0001895 9.5 TULP1 RPE65 AIPL1
5 regulation of rhodopsin mediated signaling pathway GO:0022400 9.49 GUCY2D AIPL1
6 detection of light stimulus involved in visual perception GO:0050908 9.48 TULP1 RPE65
7 vitamin A metabolic process GO:0006776 9.46 RPE65 LRAT
8 photoreceptor cell maintenance GO:0045494 9.46 TULP1 SPATA7 RDH12 LCA5
9 eye photoreceptor cell development GO:0042462 9.43 TULP1 CRB1 CEP290
10 protein localization to photoreceptor outer segment GO:1903546 9.4 TULP1 SPATA7
11 visual perception GO:0007601 9.23 TULP1 SPATA7 RPE65 RDH12 LRAT GUCY2D

Sources for Leber Congenital Amaurosis 9

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
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43 MeSH
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48 NCI
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50 NDF-RT
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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