DOA+
MCID: OPT066
MIFTS: 37

Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy (DOA+)

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

Aliases & Classifications for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

MalaCards integrated aliases for Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

Name: Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy 57 13 73
Dominant Optic Atrophy Plus Syndrome 57 75
Doa+ 57 75
Optic Atrophy with or Without Deafness Ophthalmoplegia Myopathy Ataxia and Neuropathy 75
Dominant Optic Atrophy Plus Syndrome; Doa+ 57
3-Methylglutaconic Aciduria Type 3 73
Optic Atrophy, Autosomal Dominant 73
Autosomal Dominant Optic Atrophy 53
Optic Atrophy Plus Syndrome 57
Optic Atrophy, Dominant 6
Dominant Optic Atrophy 53
Adoa 53
Doa 53

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
progressive disorder
variable age of onset (childhood to adult)


HPO:

32
optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy:
Onset and clinical course phenotypic variability progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

NIH Rare Diseases : 53 Dominant optic atrophy (DOA) is an inheritedoptic nerve disorder characterized by degeneration of the optic nerves. It typically starts during the first decade of life. Affected people usually develop moderate visual loss and color vision defects. The severity varies and visual acuity can range from normal to legal blindness. About 20% of people with DOA have non-ocular features, such as sensorineural hearing loss; myopathy; peripheral neuropathy; multiple sclerosis-like illness; and spastic paraplegia (impaired function of the legs). These cases may be referred to as 'DOA plus.' DOA is inherited in an autosomal dominant manner and may be caused by a mutation in any of several genes, some of which have not been identified. There is currently no way to prevent or cure DOA, but affected people may benefit from low vision aids.

MalaCards based summary : Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy, also known as dominant optic atrophy plus syndrome, is related to optic nerve disease and 3-methylglutaconic aciduria, type iii, and has symptoms including ataxia, abnormality of extrapyramidal motor function and ophthalmoplegia. An important gene associated with Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy is OPA1 (OPA1, Mitochondrial Dynamin Like GTPase). Affiliated tissues include eye, and related phenotypes are ptosis and nystagmus

OMIM : 57 Syndromic optic atrophy, also known as DOA+ syndrome, is a neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia (PEO), muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). (125250)

UniProtKB/Swiss-Prot : 75 Dominant optic atrophy plus syndrome: A neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes.

Related Diseases for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Graphical network of the top 20 diseases related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:



Diseases related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy

Symptoms & Phenotypes for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
optic atrophy
strabismus
central scotoma
centrocecal scotoma
more
Muscle Soft Tissue:
myopathy, mild
increased fiber size variation
mitochondrial dna deletions (in some patients)
ragged red fibers

Neurologic Peripheral Nervous System:
axonal sensorineural polyneuropathy

Head And Neck Ears:
hearing loss, progressive sensorineural
absent or decreased auditory brainstem responses
auditory neuropathy

Neurologic Central Nervous System:
cerebellar ataxia (in some patients)
spasticity (in some patients)
gait difficulties (in some patients)


Clinical features from OMIM:

125250

Human phenotypes related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

32 (show all 26)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 nystagmus 32 frequent (33%) HP:0000639
3 intellectual disability 32 frequent (33%) HP:0001249
4 ataxia 32 occasional (7.5%) HP:0001251
5 spasticity 32 occasional (7.5%) HP:0001257
6 dysarthria 32 frequent (33%) HP:0001260
7 gait disturbance 32 occasional (7.5%) HP:0001288
8 visual impairment 32 hallmark (90%) HP:0000505
9 optic atrophy 32 HP:0000648
10 myopathy 32 HP:0003198
11 peripheral neuropathy 32 HP:0009830
12 strabismus 32 HP:0000486
13 reduced visual acuity 32 HP:0007663
14 central scotoma 32 HP:0000603
15 choreoathetosis 32 hallmark (90%) HP:0001266
16 centrocecal scotoma 32 HP:0000576
17 horizontal nystagmus 32 HP:0000666
18 ophthalmoplegia 32 HP:0000602
19 increased variability in muscle fiber diameter 32 HP:0003557
20 progressive sensorineural hearing impairment 32 HP:0000408
21 spastic paraparesis 32 frequent (33%) HP:0002313
22 abnormal auditory evoked potentials 32 HP:0006958
23 3-methylglutaconic aciduria 32 hallmark (90%) HP:0003535
24 tritanomaly 32 HP:0000552
25 red-green dyschromatopsia 32 HP:0000642
26 abnormal amplitude of pattern reversal visual evoked potentials 32 HP:0000650

UMLS symptoms related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:


ataxia, abnormality of extrapyramidal motor function, ophthalmoplegia, muscle spasticity

MGI Mouse Phenotypes related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.96 OPA1 OPA3
2 craniofacial MP:0005382 8.62 OPA1 OPA3

Drugs & Therapeutics for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Search Clinical Trials , NIH Clinical Center for Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy

Genetic Tests for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Anatomical Context for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

MalaCards organs/tissues related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

41
Eye

Publications for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Articles related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

# Title Authors Year
1
Ineffectiveness of oral coenzyme Q10 supplementation in 3-methylglutaconic aciduria, type 3. ( 9533558 )
1998
2
Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. ( 9097959 )
1997
3
3-Methylglutaconic aciduria, type 3. ( 7573769 )
1995

Variations for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

UniProtKB/Swiss-Prot genetic disease variations for Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

75
# Symbol AA change Variation ID SNP ID
1 OPA1 p.Arg445His VAR_015741 rs80356529
2 OPA1 p.Ser545Arg VAR_026533 rs398124298
3 OPA1 p.Ala357Thr VAR_060836 rs190223702
4 OPA1 p.Cys551Tyr VAR_060851 rs879255592
5 OPA1 p.Tyr582Cys VAR_060853 rs121908376
6 OPA1 p.Gly439Val VAR_072127 rs387906900
7 OPA1 p.Thr449Pro VAR_072128
8 OPA1 p.Val910Asp VAR_072132 rs387906901

ClinVar genetic disease variations for Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy:

6 (show top 50) (show all 530)
# Gene Variation Type Significance SNP ID Assembly Location
1 OPA3 NM_025136.3(OPA3): c.143-1G> C single nucleotide variant Pathogenic rs80356523 GRCh37 Chromosome 19, 46057170: 46057170
2 OPA3 NM_025136.3(OPA3): c.143-1G> C single nucleotide variant Pathogenic rs80356523 GRCh38 Chromosome 19, 45553912: 45553912
3 OPA3 NM_025136.3(OPA3): c.320_337del18 (p.Gln108_Glu113del) deletion Pathogenic rs80356526 GRCh37 Chromosome 19, 46056975: 46056992
4 OPA3 NM_025136.3(OPA3): c.320_337del18 (p.Gln108_Glu113del) deletion Pathogenic rs80356526 GRCh38 Chromosome 19, 45553717: 45553734
5 OPA1 NM_015560.2(OPA1): c.1745A> G (p.Tyr582Cys) single nucleotide variant Pathogenic rs121908376 GRCh37 Chromosome 3, 193365898: 193365898
6 OPA1 NM_015560.2(OPA1): c.1745A> G (p.Tyr582Cys) single nucleotide variant Pathogenic rs121908376 GRCh38 Chromosome 3, 193648109: 193648109
7 OPA1 NM_015560.2(OPA1): c.1334G> A (p.Arg445His) single nucleotide variant Pathogenic rs80356529 GRCh37 Chromosome 3, 193361785: 193361785
8 OPA1 NM_015560.2(OPA1): c.1334G> A (p.Arg445His) single nucleotide variant Pathogenic rs80356529 GRCh38 Chromosome 3, 193643996: 193643996
9 OPA1 NM_015560.2(OPA1): c.2848_2849delGA (p.Asp950Cysfs) deletion Pathogenic rs879255513 GRCh38 Chromosome 3, 193692092: 193692093
10 OPA1 NM_015560.2(OPA1): c.2848_2849delGA (p.Asp950Cysfs) deletion Pathogenic rs879255513 GRCh37 Chromosome 3, 193409881: 193409882
11 OPA3 NM_025136.3(OPA3): c.231T> C (p.Ala77=) single nucleotide variant Benign rs3826860 GRCh37 Chromosome 19, 46057081: 46057081
12 OPA3 NM_025136.3(OPA3): c.231T> C (p.Ala77=) single nucleotide variant Benign rs3826860 GRCh38 Chromosome 19, 45553823: 45553823
13 OPA3 NM_025136.3(OPA3): c.415C> T (p.Gln139Ter) single nucleotide variant Likely pathogenic rs28937899 GRCh37 Chromosome 19, 46056897: 46056897
14 OPA3 NM_025136.3(OPA3): c.415C> T (p.Gln139Ter) single nucleotide variant Likely pathogenic rs28937899 GRCh38 Chromosome 19, 45553639: 45553639
15 OPA1 NM_015560.2(OPA1): c.1294A> G (p.Ile432Val) single nucleotide variant Pathogenic rs387906899 GRCh37 Chromosome 3, 193361398: 193361398
16 OPA1 NM_015560.2(OPA1): c.1294A> G (p.Ile432Val) single nucleotide variant Pathogenic rs387906899 GRCh38 Chromosome 3, 193643609: 193643609
17 OPA1 NM_015560.2(OPA1): c.1635C> G (p.Ser545Arg) single nucleotide variant Pathogenic rs398124298 GRCh37 Chromosome 3, 193364899: 193364899
18 OPA1 NM_015560.2(OPA1): c.1635C> G (p.Ser545Arg) single nucleotide variant Pathogenic rs398124298 GRCh38 Chromosome 3, 193647110: 193647110
19 OPA1 NM_015560.2(OPA1): c.1316G> T (p.Gly439Val) single nucleotide variant Pathogenic rs387906900 GRCh37 Chromosome 3, 193361767: 193361767
20 OPA1 NM_015560.2(OPA1): c.1316G> T (p.Gly439Val) single nucleotide variant Pathogenic rs387906900 GRCh38 Chromosome 3, 193643978: 193643978
21 OPA1 NM_015560.2(OPA1): c.2729T> A (p.Val910Asp) single nucleotide variant Pathogenic rs387906901 GRCh37 Chromosome 3, 193384980: 193384980
22 OPA1 NM_015560.2(OPA1): c.2729T> A (p.Val910Asp) single nucleotide variant Pathogenic rs387906901 GRCh38 Chromosome 3, 193667191: 193667191
23 OPA1 NM_015560.2(OPA1): c.1146A> G (p.Ile382Met) single nucleotide variant Conflicting interpretations of pathogenicity rs143319805 GRCh37 Chromosome 3, 193361167: 193361167
24 OPA1 NM_015560.2(OPA1): c.1146A> G (p.Ile382Met) single nucleotide variant Conflicting interpretations of pathogenicity rs143319805 GRCh38 Chromosome 3, 193643378: 193643378
25 OPA1 NM_015560.2(OPA1): c.1071A> G (p.Ala357=) single nucleotide variant Benign/Likely benign rs150807064 GRCh37 Chromosome 3, 193360769: 193360769
26 OPA1 NM_015560.2(OPA1): c.1071A> G (p.Ala357=) single nucleotide variant Benign/Likely benign rs150807064 GRCh38 Chromosome 3, 193642980: 193642980
27 OPA1 NM_015560.2(OPA1): c.1177A> C (p.Arg393=) single nucleotide variant Benign/Likely benign rs149752576 GRCh37 Chromosome 3, 193361198: 193361198
28 OPA1 NM_015560.2(OPA1): c.1177A> C (p.Arg393=) single nucleotide variant Benign/Likely benign rs149752576 GRCh38 Chromosome 3, 193643409: 193643409
29 OPA1 NM_015560.2(OPA1): c.1608A> C (p.Ala536=) single nucleotide variant Benign/Likely benign rs78767626 GRCh37 Chromosome 3, 193364872: 193364872
30 OPA1 NM_015560.2(OPA1): c.1608A> C (p.Ala536=) single nucleotide variant Benign/Likely benign rs78767626 GRCh38 Chromosome 3, 193647083: 193647083
31 OPA1 NM_015560.2(OPA1): c.1884A> G (p.Val628=) single nucleotide variant Benign/Likely benign rs73069703 GRCh37 Chromosome 3, 193372687: 193372687
32 OPA1 NM_015560.2(OPA1): c.1884A> G (p.Val628=) single nucleotide variant Benign/Likely benign rs73069703 GRCh38 Chromosome 3, 193654898: 193654898
33 OPA1 NM_015560.2(OPA1): c.2109T> C (p.Ala703=) single nucleotide variant Benign rs9851685 GRCh37 Chromosome 3, 193374964: 193374964
34 OPA1 NM_015560.2(OPA1): c.2109T> C (p.Ala703=) single nucleotide variant Benign rs9851685 GRCh38 Chromosome 3, 193657175: 193657175
35 OPA1 NM_015560.2(OPA1): c.254G> A (p.Arg85His) single nucleotide variant Conflicting interpretations of pathogenicity rs35630194 GRCh37 Chromosome 3, 193332733: 193332733
36 OPA1 NM_015560.2(OPA1): c.254G> A (p.Arg85His) single nucleotide variant Conflicting interpretations of pathogenicity rs35630194 GRCh38 Chromosome 3, 193614944: 193614944
37 OPA1 NM_015560.2(OPA1): c.2613+11C> G single nucleotide variant Benign/Likely benign rs111688935 GRCh37 Chromosome 3, 193382796: 193382796
38 OPA1 NM_015560.2(OPA1): c.2613+11C> G single nucleotide variant Benign/Likely benign rs111688935 GRCh38 Chromosome 3, 193665007: 193665007
39 OPA1 NM_015560.2(OPA1): c.2796C> T (p.Arg932=) single nucleotide variant Benign/Likely benign rs35540805 GRCh37 Chromosome 3, 193385047: 193385047
40 OPA1 NM_015560.2(OPA1): c.2796C> T (p.Arg932=) single nucleotide variant Benign/Likely benign rs35540805 GRCh38 Chromosome 3, 193667258: 193667258
41 OPA1 NM_015560.2(OPA1): c.321G> A (p.Ser107=) single nucleotide variant Benign/Likely benign rs117888848 GRCh37 Chromosome 3, 193332800: 193332800
42 OPA1 NM_015560.2(OPA1): c.321G> A (p.Ser107=) single nucleotide variant Benign/Likely benign rs117888848 GRCh38 Chromosome 3, 193615011: 193615011
43 OPA1 NM_130831.2(OPA1): c.420G> T (p.Val140=) single nucleotide variant Benign/Likely benign rs35801538 GRCh37 Chromosome 3, 193333531: 193333531
44 OPA1 NM_130831.2(OPA1): c.420G> T (p.Val140=) single nucleotide variant Benign/Likely benign rs35801538 GRCh38 Chromosome 3, 193615742: 193615742
45 OPA1 NM_015560.2(OPA1): c.43C> A (p.Gln15Lys) single nucleotide variant Benign/Likely benign rs75414918 GRCh37 Chromosome 3, 193332522: 193332522
46 OPA1 NM_015560.2(OPA1): c.43C> A (p.Gln15Lys) single nucleotide variant Benign/Likely benign rs75414918 GRCh38 Chromosome 3, 193614733: 193614733
47 OPA1 NM_015560.2(OPA1): c.473G> A (p.Ser158Asn) single nucleotide variant Benign rs7624750 GRCh37 Chromosome 3, 193334991: 193334991
48 OPA1 NM_015560.2(OPA1): c.473G> A (p.Ser158Asn) single nucleotide variant Benign rs7624750 GRCh38 Chromosome 3, 193617202: 193617202
49 OPA1 NM_015560.2(OPA1): c.575C> T (p.Ala192Val) single nucleotide variant Benign/Likely benign rs34307082 GRCh37 Chromosome 3, 193336676: 193336676
50 OPA1 NM_015560.2(OPA1): c.575C> T (p.Ala192Val) single nucleotide variant Benign/Likely benign rs34307082 GRCh38 Chromosome 3, 193618887: 193618887

Expression for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Search GEO for disease gene expression data for Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy.

Pathways for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

GO Terms for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

Biological processes related to Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to stimulus GO:0050896 9.16 OPA1 OPA3
2 visual perception GO:0007601 8.96 OPA1 OPA3
3 mitochondrion morphogenesis GO:0070584 8.62 OPA1 OPA3

Sources for Optic Atrophy with or Without Deafness, Ophthalmoplegia,...

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