DRPLA
MCID: DNT005
MIFTS: 53

Dentatorubral-Pallidoluysian Atrophy (DRPLA)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Dentatorubral-Pallidoluysian Atrophy

MalaCards integrated aliases for Dentatorubral-Pallidoluysian Atrophy:

Name: Dentatorubral-Pallidoluysian Atrophy 58 12 77 25 54 26 76 15 74
Drpla 58 12 25 54 26 60 76 56
Naito-Oyanagi Disease 58 12 26 60
Haw River Syndrome 58 12 54 26
Myoclonic Epilepsy with Choreoathetosis 58 54 26
Dentatorubral Pallidoluysian Atrophy 60 30 6
Dentatorubropallidoluysian Atrophy 54 60 38
Nod 58 54 26
Ataxia, Chorea, Seizures, and Dementia 58 54
Dentatorubro-Pallidoluysian Atrophy 58 13
Atrophy, Pallidoluysian, Dentatorubral 41
Myoclonic Epilepsies, Progressive 45
Naito-Oyanagi Disease; Nod 58
Haw River Syndrome; Hrs 58
Naito Oyanagi Disease 54
Hrs 58

Characteristics:

Orphanet epidemiological data:

60
dentatorubral pallidoluysian atrophy
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Japan); Age of onset: All ages;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
genetic anticipation
mean age of onset 30 years (range first to seventh decade)
phenotypic heterogeneity


HPO:

33
dentatorubral-pallidoluysian atrophy:
Inheritance genetic anticipation autosomal dominant inheritance


GeneReviews:

25
Penetrance Expanded alleles are fully penetrant except for one individual with a mildly expanded number of cag repeats (51 repeats) who was asmptomatic at age 81 years [hattori et al 1999]...

Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Dentatorubral-Pallidoluysian Atrophy

NIH Rare Diseases : 54 Dentatorubral-pallidoluysian atrophy (DRPLA) is a brain disorder that worsens over time. It can lead to involuntary movements, mental and emotional problems, and a decline in thinking ability. Symptoms usually appear around 30 years of age, but can occur anytime from infancy to mid-adulthood. Specific signs and symptoms may differ and include seizures, issues with balance and coordination (ataxia), and involuntary muscle jerking or twitching (myoclonus). Other symptoms that usually appear in adulthood include dementia and psychiatric conditions. DRPLA is caused by a mutation in the ATN1 gene and is inherited in an autosomal dominant manner. Although there is no specific treatment or cure for DRPLA, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options based on each person�??s symptoms.

MalaCards based summary : Dentatorubral-Pallidoluysian Atrophy, also known as drpla, is related to cerebellar degeneration and choreatic disease, and has symptoms including seizures, myoclonus and cerebellar ataxia. An important gene associated with Dentatorubral-Pallidoluysian Atrophy is ATN1 (Atrophin 1), and among its related pathways/superpathways are Akt Signaling and Chks in Checkpoint Regulation. Affiliated tissues include brain, heart and bone, and related phenotypes are progressive cerebellar ataxia and fetal cystic hygroma

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that has material basis in expansion of CAG triplet repeats (glutamine) encoding a polyglutamine tract in the atrophin-1 protein.

Genetics Home Reference : 26 Dentatorubral-pallidoluysian atrophy, commonly known as DRPLA, is a progressive brain disorder that causes involuntary movements, mental and emotional problems, and a decline in thinking ability. The average age of onset of DRPLA is 30 years, but this condition can appear anytime from infancy to mid-adulthood.

UniProtKB/Swiss-Prot : 76 Dentatorubral-pallidoluysian atrophy: Autosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth.

Wikipedia : 77 Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration... more...

Description from OMIM: 125370
GeneReviews: NBK1491

Related Diseases for Dentatorubral-Pallidoluysian Atrophy

Diseases related to Dentatorubral-Pallidoluysian Atrophy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 261)
# Related Disease Score Top Affiliating Genes
1 cerebellar degeneration 30.8 ATXN2 CACNA1A
2 choreatic disease 30.2 HTT JPH3
3 huntington disease 29.5 ATN1 ATXN1 ATXN3 HTT JPH3
4 machado-joseph disease 29.5 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
5 spinocerebellar ataxia 1 29.2 ATN1 ATXN1 ATXN3 ATXN7 CACNA1A HTT
6 autosomal dominant cerebellar ataxia 29.2 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A
7 aceruloplasminemia 29.0 ATXN1 ATXN2 ATXN3 ATXN7 CACNA1A PPP2R2B
8 hepatorenal syndrome 11.5
9 marie unna congenital hypotrichosis 11.5
10 unverricht-lundborg syndrome 11.4
11 progressive myoclonus epilepsy, lafora type 11.4
12 hypotrichosis 4 11.4
13 atrichia with papular lesions 11.4
14 lymphoma, hodgkin, classic 11.4
15 rh-null, amorph type 11.1
16 ramer ladda syndrome 11.1
17 aspiration pneumonitis 11.1
18 aplasia cutis congenita, nonsyndromic 10.7
19 epilepsy 10.6
20 myoclonus epilepsy 10.6
21 myoclonus 10.6
22 muscular atrophy 10.5
23 breast cancer 10.4
24 atrial fibrillation 10.4
25 supranuclear palsy, progressive, 1 10.4
26 esterase c 10.4
27 heart disease 10.3
28 myoclonus and ataxia 10.3
29 cervical dystonia 10.3
30 lymphocytic choriomeningitis 10.3
31 status epilepticus 10.3
32 ganglioglioma 10.3
33 dystonia 10.3
34 paraplegia 10.3
35 central pontine myelinolysis 10.3
36 progressive myoclonus epilepsy 10.3
37 glyceraldehyde-3-phosphate dehydrogenase deficiency 10.3
38 seizure disorder 10.3
39 tremor 10.3
40 tetralogy of fallot 10.2
41 cardiac conduction defect 10.2
42 syncope 10.2
43 cardiac arrhythmia 10.2
44 cervical cancer 10.2
45 leukemia 10.2
46 early myoclonic encephalopathy 10.2
47 multiple sclerosis 10.1
48 keratoconus 10.1
49 cervical intraepithelial neoplasia 10.1
50 schizophrenia 10.1

Graphical network of the top 20 diseases related to Dentatorubral-Pallidoluysian Atrophy:



Diseases related to Dentatorubral-Pallidoluysian Atrophy

Symptoms & Phenotypes for Dentatorubral-Pallidoluysian Atrophy

Human phenotypes related to Dentatorubral-Pallidoluysian Atrophy:

60 33 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive cerebellar ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002073
2 fetal cystic hygroma 33 hallmark (90%) HP:0010878
3 atrophy of the dentate nucleus 33 hallmark (90%) HP:0007047
4 nystagmus 60 33 very rare (1%) Frequent (79-30%) HP:0000639
5 seizures 60 33 very rare (1%) Frequent (79-30%) HP:0001250
6 dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0001260
7 myoclonus 60 33 very rare (1%) Frequent (79-30%) HP:0001336
8 gait ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002066
9 limb ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002070
10 impaired proprioception 60 33 frequent (33%) Frequent (79-30%) HP:0010831
11 dysmetria 60 33 frequent (33%) Frequent (79-30%) HP:0001310
12 ophthalmoparesis 60 33 frequent (33%) Frequent (79-30%) HP:0000597
13 dementia 60 33 very rare (1%) Frequent (79-30%) HP:0000726
14 dysdiadochokinesis 60 33 frequent (33%) Frequent (79-30%) HP:0002075
15 optic neuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0001138
16 saccadic smooth pursuit 60 33 frequent (33%) Frequent (79-30%) HP:0001152
17 hyporeflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001265
18 choreoathetosis 60 33 frequent (33%) Frequent (79-30%) HP:0001266
19 truncal ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002078
20 action tremor 60 33 frequent (33%) Frequent (79-30%) HP:0002345
21 dyssynergia 60 33 frequent (33%) Frequent (79-30%) HP:0010867
22 hyperintensity of cerebral white matter on mri 60 33 frequent (33%) Frequent (79-30%) HP:0030890
23 memory impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0002354
24 blepharospasm 60 33 occasional (7.5%) Occasional (29-5%) HP:0000643
25 oromandibular dystonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0012048
26 ataxia 60 33 very rare (1%) Frequent (79-30%) HP:0001251
27 chorea 33 very rare (1%) HP:0002072
28 abnormal pyramidal sign 33 very rare (1%) HP:0007256
29 cognitive impairment 60 Frequent (79-30%)
30 involuntary movements 60 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
myoclonus
dementia
choreoathetosis
cerebellar ataxia
more

Clinical features from OMIM:

125370

UMLS symptoms related to Dentatorubral-Pallidoluysian Atrophy:


seizures, myoclonus, cerebellar ataxia

MGI Mouse Phenotypes related to Dentatorubral-Pallidoluysian Atrophy:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.97 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 BAIAP2
2 homeostasis/metabolism MP:0005376 9.86 ATN1 ATXN1 ATXN2 ATXN3 BAIAP2 CACNA1A
3 mortality/aging MP:0010768 9.76 ATN1 ATXN1 ATXN2 ATXN7 BAIAP2 CACNA1A
4 nervous system MP:0003631 9.61 ATN1 ATXN1 ATXN2 ATXN3 ATXN7 BAIAP2
5 reproductive system MP:0005389 9.1 ATN1 ATXN2 ATXN7 CACNA1A HTT JPH3

Drugs & Therapeutics for Dentatorubral-Pallidoluysian Atrophy

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246

Search NIH Clinical Center for Dentatorubral-Pallidoluysian Atrophy

Cochrane evidence based reviews: myoclonic epilepsies, progressive

Genetic Tests for Dentatorubral-Pallidoluysian Atrophy

Genetic tests related to Dentatorubral-Pallidoluysian Atrophy:

# Genetic test Affiliating Genes
1 Dentatorubral Pallidoluysian Atrophy 30 ATN1

Anatomical Context for Dentatorubral-Pallidoluysian Atrophy

MalaCards organs/tissues related to Dentatorubral-Pallidoluysian Atrophy:

42
Brain, Heart, Bone, Prostate, Myeloid, Eye, Kidney

Publications for Dentatorubral-Pallidoluysian Atrophy

Articles related to Dentatorubral-Pallidoluysian Atrophy:

(show top 50) (show all 207)
# Title Authors Year
1
Dentatorubral-pallidoluysian Atrophy: An Update. ( 30410817 )
2018
2
Successful treatment of psychosis in dentatorubral-pallidoluysian atrophy with quetiapine: A case report. ( 30106267 )
2018
3
Successful Treatment with Olanzapine of Psychosis in Dentatorubral-pallidoluysian Atrophy: A Case Report. ( 29739138 )
2018
4
Pearls & Oy-sters: Family history of Huntington disease disguised a case of dentatorubral-pallidoluysian atrophy. ( 29335306 )
2018
5
Clinical and magnetic resonance imaging features of elderly onset dentatorubral-pallidoluysian atrophy. ( 29236168 )
2018
6
Efficacy of perampanel for controlling seizures and improving neurological dysfunction in a patient with dentatorubral-pallidoluysian atrophy (DRPLA). ( 28856097 )
2017
7
Dentatorubral-pallidoluysian atrophy (DRPLA) with a small ganglioglioma component containing neurofibrillary tangles and polyglutamine aggregation. ( 28144989 )
2017
8
Dentatorubro-Pallidoluysian Atrophy (DRPLA) among 700 Families with Ataxia in Brazil. ( 28432641 )
2017
9
Striatal glucose hypometabolism in preadolescent-onset dentatorubral-pallidoluysian atrophy. ( 26723987 )
2016
10
Teaching NeuroImages: Leukodystrophy and progressive myoclonic epilepsy disclosing DRPLA. ( 26857957 )
2016
11
Eye of the Tiger Sign and Very Late Onset in Dentatorubral-Pallidoluysian Atrophy. ( 30838235 )
2015
12
The first identified Central-Eastern European patient with genetically confirmed dentatorubral-pallidoluysian atrophy. ( 25842919 )
2015
13
Case report of optic atrophy in Dentatorubropallidoluysian Atrophy (DRPLA). ( 26679169 )
2015
14
A shared haplotype for dentatorubropallidoluysian atrophy (DRPLA) in Italian families testifies of the recent introduction of the mutation. ( 24401908 )
2014
15
Juvenile myoclonic epilepsy is not associated with the DRPLA gene in a European population. ( 25398822 )
2014
16
EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. ( 24418350 )
2014
17
Increased aggregation of polyleucine compared with that of polyglutamine in dentatorubral-pallidoluysian atrophy protein. ( 23933208 )
2013
18
Hypoalbuminemia in early onset dentatorubral-pallidoluysian atrophy due to leakage of albumin in multiple organs. ( 23263592 )
2013
19
DRPLA: recent advances in research using transgenic mouse models. ( 23754232 )
2013
20
Importance of CAG repeat length in childhood-onset dentatorubral-pallidoluysian atrophy. ( 22527233 )
2012
21
Neurological picture. Distinctive MRI abnormalities in a man with dentatorubral-pallidoluysian atrophy. ( 22362920 )
2012
22
Is cerebral white matter involvement helpful in the diagnosis of dentatorubral-pallidoluysian atrophy? ( 22286658 )
2012
23
Dentatorubral-pallidoluysian atrophy: haplotype of Asian origin in 2 Italian families. ( 22083836 )
2012
24
Dentatorubral-pallidoluysian atrophy. ( 21827919 )
2012
25
Amelioration of disabling myoclonus in a case of DRPLA by levetiracetam. ( 21889282 )
2012
26
Optineurin immunoreactivity in neuronal nuclear inclusions of polyglutamine diseases (Huntington's, DRPLA, SCA2, SCA3) and intranuclear inclusion body disease. ( 22318854 )
2012
27
DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles. ( 22342974 )
2012
28
Dentatorubral pallidoluysian atrophy. ( 21496575 )
2011
29
Transarterial embolisation for refractory bilateral chronic subdural hematomas in a case with dentatorubral-pallidoluysian atrophy. ( 21125409 )
2011
30
Radiologic and neuropathologic findings in patients in a family with dentatorubral-pallidoluysian atrophy. ( 20966051 )
2011
31
Proteolytic processing regulates pathological accumulation in dentatorubral-pallidoluysian atrophy. ( 20977674 )
2010
32
Dentatorubral pallidoluysian atrophy presenting with urinary retention. ( 20669269 )
2010
33
Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy: a correlation with CAG repeat length. ( 20589872 )
2010
34
Dentatorubral-pallidoluysian atrophy (DRPLA): The 50th Anniversary of Japanese Society of Neuropathology. ( 20500452 )
2010
35
Absence seizures with myoclonic seizures as an early manifestation of dentato-rubro-pallido-luysian atrophy (DRPLA): a follow-up clinical course of twelve years. ( 20514931 )
2010
36
The fine line between waste disposal and recycling: DRPLA fly models illustrate the importance of completing the autophagy cycle for rescuing neurodegeneration. ( 20543566 )
2010
37
[Polynucleotide repeat expansion of nine spinocerebellar ataxia subtypes and dentatorubral-pallidoluysian atrophy in healthy Chinese Han population]. ( 20931525 )
2010
38
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. ( 20050888 )
2010
39
A case of late adult-onset dentatorubral-pallidoluysian atrophy mimicking central pontine myelinolysis. ( 19390768 )
2009
40
Dentatorubral pallidoluysian atrophy in a Turkish family. ( 20196398 )
2009
41
Clinical and genetic characteristics of non-Asian dentatorubral-pallidoluysian atrophy: A systematic review. ( 19514013 )
2009
42
Cutaneous accumulation of abnormal polyglutamine proteins of patients with dentatorubral-pallidoluysian atrophy. ( 19469833 )
2009
43
Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice. ( 19039037 )
2009
44
[Case report of dentatorubral pallidoluysian atrophy in a patient on a ketogenic diet]. ( 19522273 )
2009
45
Electroclinical features of epilepsy in patients with juvenile type dentatorubral-pallidoluysian atrophy. ( 18616556 )
2008
46
Dentatorubral pallidoluysian atrophy in South Wales. ( 17965145 )
2008
47
Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy. ( 17949751 )
2008
48
Neuropathological analysis of the brainstem and cerebral cortex lesions on epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy. ( 17307319 )
2007
49
Renal complications in two patients with dentatorubral-pallidoluysian atrophy. ( 17269599 )
2007
50
Rapidly progressive sporadic dentatorubral pallidoluysian atrophy with intracytoplasmic inclusions and no CAG repeat expansion. ( 17078058 )
2006

Variations for Dentatorubral-Pallidoluysian Atrophy

ClinVar genetic disease variations for Dentatorubral-Pallidoluysian Atrophy:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ATN1; LOC109461484 NM_001007026.1(ATN1): c.1462CAG[(49_55)] (p.Gln488[(49-55)]) NT expansion Pathogenic rs60216939 GRCh37 Chromosome 12, 7045892: 7045894
2 ATN1; LOC109461484 NM_001007026.1(ATN1): c.1462CAG[(49_55)] (p.Gln488[(49-55)]) NT expansion Pathogenic rs60216939 GRCh38 Chromosome 12, 6936729: 6936731
3 ATN1; LOC109461484 NM_001007026.1(ATN1): c.1462CAG[(6_35)] (p.Gln488[(6-35)]) NT expansion Benign rs60216939 GRCh37 Chromosome 12, 7045892: 7045894
4 ATN1; LOC109461484 NM_001007026.1(ATN1): c.1462CAG[(6_35)] (p.Gln488[(6-35)]) NT expansion Benign rs60216939 GRCh38 Chromosome 12, 6936729: 6936731
5 ATN1; LOC109461484 NM_001007026.1(ATN1): c.1462CAG[(90_93)] (p.Gln488[(90-93)]) NT expansion Pathogenic rs60216939 GRCh37 Chromosome 12, 7045892: 7045894
6 ATN1; LOC109461484 NM_001007026.1(ATN1): c.1462CAG[(90_93)] (p.Gln488[(90-93)]) NT expansion Pathogenic rs60216939 GRCh38 Chromosome 12, 6936729: 6936731
7 ATN1 NM_001007026.1(ATN1): c.1462CAG[17] (p.Gln488[17]) NT expansion Conflicting interpretations of pathogenicity rs60216939 GRCh37 Chromosome 12, 7045880: 7045880
8 ATN1 NM_001007026.1(ATN1): c.1462CAG[17] (p.Gln488[17]) NT expansion Conflicting interpretations of pathogenicity rs60216939 GRCh38 Chromosome 12, 6936729: 6936729
9 NM_001007026.1: c.1462CAG[(48_93)] NT expansion Pathogenic
10 ATN1 NG_008047.1: g.17267CAG[(54-68)] NT expansion Pathogenic

Expression for Dentatorubral-Pallidoluysian Atrophy

Search GEO for disease gene expression data for Dentatorubral-Pallidoluysian Atrophy.

Pathways for Dentatorubral-Pallidoluysian Atrophy

Pathways related to Dentatorubral-Pallidoluysian Atrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.25 ATXN1 ATXN2 ATXN3 ATXN7 HTT PPP2R2B
2
Show member pathways
11.86 ATXN1 ATXN2 ATXN3 ATXN7

GO Terms for Dentatorubral-Pallidoluysian Atrophy

Cellular components related to Dentatorubral-Pallidoluysian Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.92 ATN1 ATXN1 ATXN2 ATXN3 BAIAP2 CACNA1A
2 postsynaptic cytosol GO:0099524 9.26 BAIAP2 HTT
3 presynaptic cytosol GO:0099523 9.16 BAIAP2 HTT
4 nuclear inclusion body GO:0042405 8.96 ATXN1 ATXN3
5 nuclear matrix GO:0016363 8.92 ATN1 ATXN1 ATXN3 ATXN7

Biological processes related to Dentatorubral-Pallidoluysian Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 learning GO:0007612 9.32 ATXN1 JPH3
2 regulation of phosphoprotein phosphatase activity GO:0043666 9.26 HTT PPP2R2B
3 neuromuscular process controlling balance GO:0050885 9.16 CACNA1A JPH3
4 regulation of synaptic plasticity GO:0048167 8.96 BAIAP2 JPH3
5 exploration behavior GO:0035640 8.62 ATXN3 JPH3

Molecular functions related to Dentatorubral-Pallidoluysian Atrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein C-terminus binding GO:0008022 8.8 ATXN1 ATXN2 BAIAP2

Sources for Dentatorubral-Pallidoluysian Atrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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20 FMA
29 GO
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31 HGMD
32 HMDB
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35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
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45 MeSH
46 MESH via Orphanet
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50 NCI
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59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
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75 UMLS via Orphanet
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