MCID: OPT053
MIFTS: 45

Optic Atrophy 1

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

Aliases & Classifications for Optic Atrophy 1

MalaCards integrated aliases for Optic Atrophy 1:

Name: Optic Atrophy 1 53 49 71 13
Optic Atrophy, Kjer Type 53 49 24
Optic Atrophy, Juvenile 53 49 24
Kjer-Type Optic Atrophy 53 49 71
Opa1 53 49 71
Oak 53 49 71
Optic Atrophy, Autosomal Dominant 24 69
Optic Atrophy Type 1 23 24
Optic Atrophy, Hereditary, Autosomal Dominant 24
Autosomal Dominant Optic Atrophy Kjer Type 24
Autosomal Dominant Optic Atrophy 24
Optic Atrophy Autosomal Dominant 51
Optic Atrophy, Kjer Type; Oak 53
Kjer Type Optic Atrophy 24
Optic Atrophy Kjer Type 71
Dominant Optic Atrophy 24
Optic Atrophy Juvenile 71
Kjer's Optic Atrophy 24
Adoa 24
Doa 24

Characteristics:

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
incomplete penetrance
phenotypic variability
insidious onset
bimodal onset in early childhood (median 5 years) and young adulthood (21 to 30 years)
prevalence ranges from 1 in 12,000 to 1 in 50,000
see also optic atrophy with deafness , an allelic disorder


HPO:

31
optic atrophy 1:
Onset and clinical course incomplete penetrance insidious onset
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance The estimated penetrance of 98% in opa1 has been revised in the light of molecular genetic studies. penetrance varies from family to family and pathogenic variant to pathogenic variant. it has been reported as high as 100% (variant c.1065+1g>t, resulting in exon 12 skipping) [thiselton et al 2002] and as low as 43% (variant c.2708_2711delttag in exon 27) [toomes et al 2001]. in these two studies the clinical diagnosis was made on the basis of reduced visual acuity, abnormal color discrimination, fundus examination showing temporal pallor of the optic disc, and electrophysiology studies [toomes et al 2001, thiselton et al 2002]...

Classifications:



Summaries for Optic Atrophy 1

NIH Rare Diseases : 49 Optic atrophy 1 is a condition that mainly affects vision, but may include other features. Vision loss typically begins within the first decade of life; severity varies widely among affected people (from nearly normal vision to complete blindness), even among members of the same family. Vision problems may include difficulty distinguishing colors, progressive narrowing of the field of vision (tunnel vision) and an abnormally pale appearance (pallor) of the optic nerve. Additional, less common abnormalities may include sensorineural hearing loss, ataxia, myopathy (muscle disease) and other neurological findings. It is usually caused by mutations in the OPA1 gene, although some individuals with optic atrophy 1 do not have identified mutations in this gene, in which case the cause of the condition is unknown. This condition is inherited in an autosomal dominant pattern but some cases result from a new mutation in the gene and occur in people with no history of the disorder in their family. Treatment focuses on individual symptoms when possible. Last updated: 12/22/2010

MalaCards based summary : Optic Atrophy 1, also known as optic atrophy, kjer type, is related to autosomal dominant optic atrophy plus syndrome and optic atrophy 1 and deafness, and has symptoms including ataxia, visual impairment and optic atrophy. An important gene associated with Optic Atrophy 1 is OPA1 (OPA1, Mitochondrial Dynamin Like GTPase), and among its related pathways/superpathways is Apoptosis and Autophagy. Affiliated tissues include eye, retina and lung.

OMIM : 53 Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998). Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see 125250. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). Yu-Wai-Man et al. (2009) provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON; 535000), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. (165500)

UniProtKB/Swiss-Prot : 71 Optic atrophy 1: A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA1 is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disk pallor, color vision deficits, and centrocecal scotoma of variable density.

Genetics Home Reference : 24 Optic atrophy type 1 is a condition that often causes slowly worsening vision, usually beginning in childhood. People with optic atrophy type 1 typically experience a narrowing of their field of vision (tunnel vision). Affected individuals gradually lose their sight as their field of vision becomes smaller. Both eyes are usually affected equally, but the severity of the vision loss varies widely, even among affected members of the same family, ranging from nearly normal vision to complete blindness.

GeneReviews: NBK1248

Related Diseases for Optic Atrophy 1

Graphical network of the top 20 diseases related to Optic Atrophy 1:



Diseases related to Optic Atrophy 1

Symptoms & Phenotypes for Optic Atrophy 1

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
optic atrophy
central scotoma
centrocecal scotoma
red-green dyschromatopsia
decreased visual acuity
more

Clinical features from OMIM:

165500

Human phenotypes related to Optic Atrophy 1:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 very rare (1%) HP:0001251
2 visual impairment 31 HP:0000505
3 optic atrophy 31 HP:0000648
4 strabismus 31 very rare (1%) HP:0000486
5 reduced visual acuity 31 HP:0007663
6 progressive external ophthalmoplegia 31 very rare (1%) HP:0000590
7 central scotoma 31 HP:0000603
8 centrocecal scotoma 31 HP:0000576
9 proximal muscle weakness 31 very rare (1%) HP:0003701
10 horizontal nystagmus 31 very rare (1%) HP:0000666
11 tritanomaly 31 HP:0000552
12 red-green dyschromatopsia 31 HP:0000642
13 abnormal amplitude of pattern reversal visual evoked potentials 31 HP:0000650

Drugs & Therapeutics for Optic Atrophy 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Expression of Optic Atrophy Type 1 (OPA1) Protein in Lung Adenocarcinoma Unknown status NCT01249053
2 Advanced Characterization of Autosomal Dominant Optic Atrophy Unknown status NCT01522638
3 Transcorneal Electrical Stimulation Therapy for Retinal Disease Completed NCT00804102
4 ORBERA™ Post-Approval Study Recruiting NCT02828657
5 Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
6 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Optic Atrophy 1

Genetic Tests for Optic Atrophy 1

Anatomical Context for Optic Atrophy 1

MalaCards organs/tissues related to Optic Atrophy 1:

38
Eye, Retina, Lung, Brain, T Cells

Publications for Optic Atrophy 1

Articles related to Optic Atrophy 1:

(show all 12)
# Title Authors Year
1
A Plasma Metabolomic Signature Involving Purine Metabolism in Human Optic Atrophy 1 (OPA1)-Related Disorders. ( 29340645 )
2018
2
T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression. ( 28630277 )
2017
3
Mitofusin 1 and optic atrophy 1 shift metabolism to mitochondrial respiration during aging. ( 28758339 )
2017
4
Optic atrophy 1 mediates coenzyme Q-responsive regulation of respiratory complex IV activity in brain mitochondria. ( 28890359 )
2017
5
Generation of optic atrophy 1 patient-derived induced pluripotent stem cells (iPS-OPA1-BEHR) for disease modeling of complex optic atrophy syndromes (Behr syndrome). ( 27879217 )
2016
6
Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation. ( 27585216 )
2016
7
Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control. ( 27974214 )
2016
8
Mutation survey of the optic atrophy 1 gene in 193 Chinese families with suspected hereditary optic neuropathy. ( 23401657 )
2013
9
Optic atrophy 1 mediates mitochondria remodeling and dopaminergic neurodegeneration linked to complex I deficiency. ( 22858546 )
2013
10
Overexpression of optic atrophy 1 protein increases cisplatin resistance via inactivation of caspase-dependent apoptosis in lung adenocarcinoma cells. ( 21798574 )
2012
11
Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis. ( 21983901 )
2011
12
The mitochondrial inner membrane GTPase, optic atrophy 1 (Opa1), restores mitochondrial morphology and promotes neuronal survival following excitotoxicity. ( 21041314 )
2011

Variations for Optic Atrophy 1

UniProtKB/Swiss-Prot genetic disease variations for Optic Atrophy 1:

71 (show all 49)
# Symbol AA change Variation ID SNP ID
1 OPA1 p.Arg290Gln VAR_011483 rs121908375
2 OPA1 p.Gly300Glu VAR_011484 rs28939082
3 OPA1 p.Arg445His VAR_015741 rs80356529
4 OPA1 p.Leu396Arg VAR_022927 rs727504060
5 OPA1 p.Thr503Lys VAR_022928
6 OPA1 p.Arg571His VAR_022929 rs140606054
7 OPA1 p.Ser545Arg VAR_026533 rs398124298
8 OPA1 p.Leu939Pro VAR_028370
9 OPA1 p.Ala8Ser VAR_060825 rs794726939
10 OPA1 p.Tyr80Cys VAR_060826 rs151103940
11 OPA1 p.Thr95Met VAR_060827 rs201214736
12 OPA1 p.Tyr102Cys VAR_060828 rs530896300
13 OPA1 p.Glu270Lys VAR_060829
14 OPA1 p.Leu272Pro VAR_060830
15 OPA1 p.Asp273Ala VAR_060831
16 OPA1 p.Arg290Trp VAR_060832 rs780333963
17 OPA1 p.Gln310Arg VAR_060834 rs770966290
18 OPA1 p.Ala357Thr VAR_060836 rs190223702
19 OPA1 p.Ile382Met VAR_060837 rs143319805
20 OPA1 p.Leu384Phe VAR_060838
21 OPA1 p.Leu396Pro VAR_060839
22 OPA1 p.Asn430Asp VAR_060841
23 OPA1 p.Asp438Val VAR_060842
24 OPA1 p.Thr449Arg VAR_060843
25 OPA1 p.Lys468Glu VAR_060845
26 OPA1 p.Asp470Gly VAR_060846
27 OPA1 p.Glu487Lys VAR_060847
28 OPA1 p.Lys505Asn VAR_060848
29 OPA1 p.Cys551Tyr VAR_060851 rs879255592
30 OPA1 p.Leu574Pro VAR_060852
31 OPA1 p.Arg590Gln VAR_060854 rs147077380
32 OPA1 p.Arg590Trp VAR_060855 rs778998909
33 OPA1 p.Leu593Pro VAR_060856
34 OPA1 p.Ser646Leu VAR_060857
35 OPA1 p.Asn728Lys VAR_060859
36 OPA1 p.Gly768Asp VAR_060860
37 OPA1 p.Arg781Trp VAR_060861 rs190235251
38 OPA1 p.Gln785Arg VAR_060862
39 OPA1 p.Ser823Tyr VAR_060863
40 OPA1 p.Tyr841Cys VAR_060864
41 OPA1 p.Arg882Leu VAR_060865
42 OPA1 p.Leu887Pro VAR_060866
43 OPA1 p.Arg932Cys VAR_060868 rs145710079
44 OPA1 p.Leu949Pro VAR_060869
45 OPA1 p.Pro400Ala VAR_067355
46 OPA1 p.Thr330Ser VAR_072125
47 OPA1 p.Val377Ile VAR_072126 rs780922750
48 OPA1 p.Gly439Val VAR_072127 rs387906900
49 OPA1 p.Gly459Glu VAR_072129

ClinVar genetic disease variations for Optic Atrophy 1:

6 (show all 43)
# Gene Variation Type Significance SNP ID Assembly Location
1 OPA1 NM_015560.2(OPA1): c.1065+1G> T single nucleotide variant Pathogenic rs80356528 GRCh37 Chromosome 3, 193360635: 193360635
2 OPA1 NM_015560.2(OPA1): c.1294A> G (p.Ile432Val) single nucleotide variant Pathogenic rs387906899 GRCh37 Chromosome 3, 193361398: 193361398
3 OPA1 NM_015560.2(OPA1): c.1635C> G (p.Ser545Arg) single nucleotide variant Pathogenic rs398124298 GRCh37 Chromosome 3, 193364899: 193364899
4 OPA1 NM_015560.2(OPA1): c.1316G> T (p.Gly439Val) single nucleotide variant Pathogenic rs387906900 GRCh37 Chromosome 3, 193361767: 193361767
5 OPA1 NM_015560.2(OPA1): c.2729T> A (p.Val910Asp) single nucleotide variant Pathogenic rs387906901 GRCh37 Chromosome 3, 193384980: 193384980
6 OPA1 NM_130837.2(OPA1): c.740G> A (p.Arg247His) single nucleotide variant Pathogenic rs138350727 GRCh37 Chromosome 3, 193343942: 193343942
7 OPA1 NM_015560.2(OPA1): c.1352delT (p.Leu451Trpfs) deletion Pathogenic rs398124297 GRCh37 Chromosome 3, 193361803: 193361803
8 OPA1 NM_015560.2(OPA1): c.1635C> A (p.Ser545Arg) single nucleotide variant Pathogenic rs398124298 GRCh37 Chromosome 3, 193364899: 193364899
9 OPA1 NM_015560.2(OPA1): c.1669C> T (p.Arg557Ter) single nucleotide variant Pathogenic rs398124299 GRCh37 Chromosome 3, 193364933: 193364933
10 OPA1 NM_015560.2(OPA1): c.2257C> T (p.Gln753Ter) single nucleotide variant Pathogenic rs398124301 GRCh37 Chromosome 3, 193376766: 193376766
11 OPA1 NM_015560.2(OPA1): c.983A> G (p.Lys328Arg) single nucleotide variant Pathogenic rs398124303 GRCh37 Chromosome 3, 193355853: 193355853
12 OPA1 NM_015560.2(OPA1): c.1187T> G (p.Leu396Arg) single nucleotide variant Pathogenic rs727504060 GRCh38 Chromosome 3, 193643419: 193643419
13 OPA1 NM_015560.2(OPA1): c.533T> A (p.Leu178Ter) single nucleotide variant Pathogenic rs727504058 GRCh37 Chromosome 3, 193335051: 193335051
14 OPA1 NM_015560.2(OPA1): c.870+1G> A single nucleotide variant Pathogenic rs727504059 GRCh37 Chromosome 3, 193355071: 193355071
15 OPA1 NM_015560.2(OPA1): c.2883A> C (p.Ter961Tyr) single nucleotide variant Likely pathogenic rs143929819 GRCh37 Chromosome 3, 193409916: 193409916
16 OPA1 NM_015560.2(OPA1): c.1199C> T (p.Pro400Leu) single nucleotide variant Likely pathogenic rs794727069 GRCh37 Chromosome 3, 193361220: 193361220
17 OPA1 NM_015560.2(OPA1): c.292_301delTTAAAACTTC (p.Leu98Alafs) deletion Pathogenic rs794727289 GRCh37 Chromosome 3, 193332771: 193332780
18 OPA1 NM_015560.2(OPA1): c.2059_2060delGA (p.Glu687Thrfs) deletion Pathogenic rs794727345 GRCh37 Chromosome 3, 193374914: 193374915
19 OPA1 NM_015560.2(OPA1): c.2496+1G> T single nucleotide variant Pathogenic rs794727392 GRCh37 Chromosome 3, 193380752: 193380752
20 OPA1 NM_015560.2(OPA1): c.2569C> T (p.Arg857Ter) single nucleotide variant Pathogenic rs794727405 GRCh37 Chromosome 3, 193382741: 193382741
21 OPA1 NM_015560.2(OPA1): c.635_636delAA (p.Lys212Argfs) deletion Pathogenic rs794727804 GRCh37 Chromosome 3, 193349411: 193349412
22 OPA1 NM_015560.2(OPA1): c.899G> A (p.Gly300Glu) single nucleotide variant Pathogenic rs28939082 GRCh37 Chromosome 3, 193355769: 193355769
23 OPA1 NM_015560.2(OPA1): c.985-1G> A single nucleotide variant Pathogenic rs879255510 GRCh38 Chromosome 3, 193642764: 193642764
24 OPA1 NM_015560.2(OPA1): c.2708_2711delTTAG (p.Val903Glyfs) deletion Pathogenic rs80356530 GRCh37 Chromosome 3, 193384959: 193384962
25 OPA1 NM_015560.2(OPA1): c.2825_2828delTTAG (p.Val942Glufs) deletion Pathogenic rs879255560 GRCh37 Chromosome 3, 193409858: 193409861
26 OPA1 NM_015560.2(OPA1): c.869G> A (p.Arg290Gln) single nucleotide variant Pathogenic rs121908375 GRCh37 Chromosome 3, 193355069: 193355069
27 OPA1 NM_015560.2(OPA1): c.1096C> T (p.Arg366Ter) single nucleotide variant Pathogenic rs104893753 GRCh37 Chromosome 3, 193360794: 193360794
28 OPA1 NM_015560.2(OPA1): c.1296_1298delCAT (p.Ile433del) deletion Pathogenic rs879255511 GRCh37 Chromosome 3, 193361400: 193361402
29 OPA1 NM_015560.2(OPA1): c.1354delG (p.Val452Serfs) deletion Pathogenic rs879255512 GRCh38 Chromosome 3, 193644016: 193644016
30 OPA1 NM_015560.2(OPA1): c.2826delT (p.Arg943Glufs) deletion Pathogenic rs80356531 GRCh37 Chromosome 3, 193409859: 193409859
31 OPA1 NM_015560.2(OPA1): c.1745A> G (p.Tyr582Cys) single nucleotide variant Pathogenic rs121908376 GRCh37 Chromosome 3, 193365898: 193365898
32 OPA1 NM_015560.2(OPA1): c.1334G> A (p.Arg445His) single nucleotide variant Pathogenic rs80356529 GRCh37 Chromosome 3, 193361785: 193361785
33 OPA1 NM_015560.2(OPA1): c.2848_2849delGA (p.Asp950Cysfs) deletion Pathogenic rs879255513 GRCh38 Chromosome 3, 193692092: 193692093
34 OPA1 NM_015560.2(OPA1): c.2131C> T (p.Arg711Ter) single nucleotide variant Likely pathogenic rs863224906 GRCh37 Chromosome 3, 193374986: 193374986
35 OPA1 NM_015560.2(OPA1): c.728T> A (p.Leu243Ter) single nucleotide variant Pathogenic rs863225274 GRCh37 Chromosome 3, 193353256: 193353256
36 OPA1 NM_015560.2(OPA1): c.1067_1068dupTT (p.Ala357Leufs) duplication Pathogenic rs863225275 GRCh37 Chromosome 3, 193360765: 193360766
37 OPA1 NM_015560.2(OPA1): c.1202G> A (p.Gly401Asp) single nucleotide variant Pathogenic rs863225276 GRCh37 Chromosome 3, 193361223: 193361223
38 OPA1 NM_015560.2(OPA1): c.1310A> G (p.Gln437Arg) single nucleotide variant Pathogenic rs863225277 GRCh37 Chromosome 3, 193361414: 193361414
39 OPA1 NM_130837.2(OPA1): c.1817G> A (p.Cys606Tyr) single nucleotide variant Pathogenic rs879255592 GRCh37 Chromosome 3, 193364916: 193364916
40 OPA1 NM_015560.2(OPA1): c.985-2A> G single nucleotide variant Pathogenic rs886041317 GRCh37 Chromosome 3, 193360552: 193360552
41 OPA1 NM_015560.2(OPA1): c.1140+1G> A single nucleotide variant Pathogenic rs745927258 GRCh37 Chromosome 3, 193360839: 193360839
42 OPA1 NM_015560.2(OPA1): c.2822_2823delAA (p.Lys941Serfs) deletion Pathogenic rs886043136 GRCh37 Chromosome 3, 193409855: 193409856
43 OPA1 NM_130837.2(OPA1): c.2816dupA (p.Arg940Alafs) duplication Pathogenic rs886043317 GRCh37 Chromosome 3, 193384122: 193384122

Expression for Optic Atrophy 1

Search GEO for disease gene expression data for Optic Atrophy 1.

Pathways for Optic Atrophy 1

Pathways related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.89 CYCS OPA1

GO Terms for Optic Atrophy 1

Cellular components related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial outer membrane GO:0005741 9.26 MFN2 OPA1
2 mitochondrion GO:0005739 9.26 CYCS DNM3 MFN2 OPA1
3 mitochondrial membrane GO:0031966 9.16 DNM3 OPA1
4 mitochondrial intermembrane space GO:0005758 8.62 CYCS OPA1

Biological processes related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apoptotic process GO:0006915 9.5 CYCS MFN2 OPA1
2 mitochondrion organization GO:0007005 9.26 CYCS OPA1
3 mitochondrial fission GO:0000266 9.16 DNM3 OPA1
4 mitochondrial fusion GO:0008053 8.96 MFN2 OPA1
5 dynamin family protein polymerization involved in mitochondrial fission GO:0003374 8.62 DNM3 OPA1

Molecular functions related to Optic Atrophy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule binding GO:0008017 9.16 DNM3 OPA1
2 GTP binding GO:0005525 9.13 DNM3 MFN2 OPA1
3 GTPase activity GO:0003924 8.8 DNM3 MFN2 OPA1

Sources for Optic Atrophy 1

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