PARK14
MCID: PRK071
MIFTS: 42

Parkinson Disease 14, Autosomal Recessive (PARK14)

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

Aliases & Classifications for Parkinson Disease 14, Autosomal Recessive

MalaCards integrated aliases for Parkinson Disease 14, Autosomal Recessive:

Name: Parkinson Disease 14, Autosomal Recessive 57 20 71
Parkinson Disease 14 73 29 13 6
Park14 57 20 58 73
Dystonia-Parkinsonism, Adult-Onset 57 20 44
Dystonia-Parkinsonism, Paisan-Ruiz Type 20 58
Pla2g6-Related Dystonia-Parkinsonism 20 58
Dystonia-Parkinsonism Adult-Onset 12 73
Adult-Onset Dystonia-Parkinsonism 20 58
Parkinson's Disease 14 12 15
Autosomal Recessive Parkinson's Disease 14 12
Autosomal Recessive Parkinson Disease 14 12
Parkinson Disease 14 Autosomal Recessive 73
Dystonia-Parkinsonism Paisan-Ruiz Type 73
Parkinson Disease, Type 14 39
Nbia/dyt/park-Pla2g6 20

Characteristics:

Orphanet epidemiological data:

58
adult-onset dystonia-parkinsonism
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult;

OMIM®:

57 (Updated 05-Mar-2021)
Miscellaneous:
rapidly progressive
onset in young adulthood
favorable initial response to l-dopa
foot dragging may appear in childhood
l-dopa-induced dyskinesias

Inheritance:
autosomal recessive


HPO:

31
parkinson disease 14, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course rapidly progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Parkinson Disease 14, Autosomal Recessive

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 199351DefinitionA rare neurodegenerative disease usually presenting before the age of 30 and which is characterized by dystonia, L-dopa-responsive parkinsonism, pyramidal signs and rapid cognitive decline.EpidemiologyPrevalence is unknown. Only 14 cases have been reported to date.Clinical descriptionDisease onset occurs in late adolescence or early adulthood (usually before the age of 30) and usually presents with parkinsonism (tremor, rigidity, bradykinesia), dystonia and rapid cognitive decline. Eye movement abnormalities (supranuclear vertical gaze palsy, eyelid opening apraxia), pyramidal tract signs, and psychiatric features such as depression and personality changes have also been reported in some patients. Dopaminergic treatment is initially successful with regard to parkinsonism, but the development of prominent dyskinesias often follows.EtiologyAdult-onset dystonia-parkinsonism is caused by mutations in the phospholipase A2, group VI (PLA2G6) gene located on chromosome 22q13.1.Genetic counselingAdult-onset dystonia-parkinsonism is inherited in an autosomal recessive manner, and genetic counseling is possible and recommended.Visit the Orphanet disease page for more resources.

MalaCards based summary : Parkinson Disease 14, Autosomal Recessive, also known as parkinson disease 14, is related to parkinsonism and neurodegeneration with brain iron accumulation, and has symptoms including tremor, abnormality of extrapyramidal motor function and clumsiness. An important gene associated with Parkinson Disease 14, Autosomal Recessive is PLA2G6 (Phospholipase A2 Group VI), and among its related pathways/superpathways is G alpha (s) signalling events. Affiliated tissues include eye and brain, and related phenotypes are spasticity and hyperreflexia

Disease Ontology : 12 A late-onset Parkinson disease that has material basis in homozygous mutation in the PLA2G6 gene on chromosome 22q13.

UniProtKB/Swiss-Prot : 73 Parkinson disease 14: An adult-onset progressive neurodegenerative disorder characterized by parkinsonism, dystonia, severe cognitive decline, cerebral and cerebellar atrophy and absent iron in the basal ganglia on magnetic resonance imaging.

More information from OMIM: 612953 PS168600

Related Diseases for Parkinson Disease 14, Autosomal Recessive

Diseases in the Parkinson Disease, Late-Onset family:

Parkinson Disease 1, Autosomal Dominant Parkinson Disease 15, Autosomal Recessive Early-Onset
Parkinson Disease 12 Parkinson Disease 2, Autosomal Recessive Juvenile
Parkinson Disease 3, Autosomal Dominant Parkinson Disease 4, Autosomal Dominant
Parkinson Disease 6, Autosomal Recessive Early-Onset Parkinson Disease 7, Autosomal Recessive Early-Onset
Parkinson Disease 10 Parkinson Disease 8, Autosomal Dominant
Parkinson Disease 11, Autosomal Dominant Parkinson Disease 13, Autosomal Dominant
Parkinson Disease 14, Autosomal Recessive Parkinson Disease 16
Parkinson Disease 5, Autosomal Dominant Parkinson Disease 17
Parkinson Disease 18, Autosomal Dominant Parkinson Disease 19a, Juvenile-Onset
Parkinson Disease 20, Early-Onset Parkinson Disease 21
Parkinson Disease 22, Autosomal Dominant Parkinson Disease 23, Autosomal Recessive Early-Onset
Juvenile-Onset Parkinson's Disease Early-Onset Parkinson's Disease
Vps35-Related Parkinson Disease Hereditary Late-Onset Parkinson Disease

Diseases related to Parkinson Disease 14, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 parkinsonism 10.2
2 neurodegeneration with brain iron accumulation 10.1
3 multiple system atrophy 1 10.0
4 dystonia 10.0
5 parkinson disease, late-onset 9.9
6 neurodegeneration with brain iron accumulation 2a 9.9
7 dystonia, juvenile-onset 9.9
8 early-onset parkinson's disease 9.9
9 neuroaxonal dystrophy 9.9
10 karak syndrome 9.9
11 migraine with or without aura 1 9.6 VIPR1 CRH
12 intrahepatic cholestasis of pregnancy 9.6 NR1H4 CRH

Graphical network of the top 20 diseases related to Parkinson Disease 14, Autosomal Recessive:



Diseases related to Parkinson Disease 14, Autosomal Recessive

Symptoms & Phenotypes for Parkinson Disease 14, Autosomal Recessive

Human phenotypes related to Parkinson Disease 14, Autosomal Recessive:

58 31 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
2 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
3 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
4 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
5 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
6 dyslexia 58 31 frequent (33%) Frequent (79-30%) HP:0010522
7 clumsiness 58 31 frequent (33%) Frequent (79-30%) HP:0002312
8 rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0002063
9 generalized cerebral atrophy/hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0007058
10 postural instability 58 31 frequent (33%) Frequent (79-30%) HP:0002172
11 bradykinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002067
12 progressive extrapyramidal movement disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007153
13 hypomimic face 58 31 frequent (33%) Frequent (79-30%) HP:0000338
14 frontotemporal dementia 58 31 frequent (33%) Frequent (79-30%) HP:0002145
15 neurofibrillary tangles 58 31 frequent (33%) Frequent (79-30%) HP:0002185
16 frontotemporal cerebral atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0006892
17 focal dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0004373
18 parkinsonism with favorable response to dopaminergic medication 58 31 frequent (33%) Frequent (79-30%) HP:0002548
19 hypometric saccades 58 31 frequent (33%) Frequent (79-30%) HP:0000571
20 eyelid apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0000658
21 stiff hip 58 31 frequent (33%) Frequent (79-30%) HP:0025262
22 abnormal circulating creatine kinase concentration 31 frequent (33%) HP:0040081
23 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
24 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
25 myoclonus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001336
26 iron accumulation in brain 58 31 occasional (7.5%) Occasional (29-5%) HP:0012675
27 personality changes 58 31 occasional (7.5%) Occasional (29-5%) HP:0000751
28 paranoia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011999
29 supranuclear gaze palsy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000605
30 seizure 31 occasional (7.5%) HP:0001250
31 dystonia 58 31 Occasional (29-5%) HP:0001332
32 seizures 58 Occasional (29-5%)
33 elevated serum creatine kinase 31 HP:0003236
34 abnormal levels of creatine kinase in blood 58 Frequent (79-30%)
35 aggressive behavior 31 HP:0000718
36 parkinsonism 31 HP:0001300
37 apraxia 31 HP:0002186
38 global brain atrophy 31 HP:0002283
39 delusions 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
dysarthria
tremor
dystonia
more
Head And Neck Eyes:
supranuclear gaze palsy
eyelid opening apraxia
hypometric vertical saccades

Head And Neck Face:
facial hypomimia

Neurologic Behavioral Psychiatric Manifestations:
personality changes
depression
aggression

Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM®:

612953 (Updated 05-Mar-2021)

UMLS symptoms related to Parkinson Disease 14, Autosomal Recessive:


tremor, abnormality of extrapyramidal motor function, clumsiness, personality changes, bradykinesia, muscle rigidity, muscle spasticity

MGI Mouse Phenotypes related to Parkinson Disease 14, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.46 CRH NR1H4 P4HB VIPR1
2 growth/size/body region MP:0005378 9.35 CRH NR1H4 P4HB PLA2G6 VIPR1
3 homeostasis/metabolism MP:0005376 9.02 CRH NR1H4 P4HB PLA2G6 VIPR1

Drugs & Therapeutics for Parkinson Disease 14, Autosomal Recessive

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Unlocking Dystonia From Parkinson's Disease With Directional DBS Technology Enrolling by invitation NCT03409120

Search NIH Clinical Center for Parkinson Disease 14, Autosomal Recessive

Cochrane evidence based reviews: dystonia-parkinsonism, adult-onset

Genetic Tests for Parkinson Disease 14, Autosomal Recessive

Genetic tests related to Parkinson Disease 14, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Parkinson Disease 14 29 PLA2G6

Anatomical Context for Parkinson Disease 14, Autosomal Recessive

MalaCards organs/tissues related to Parkinson Disease 14, Autosomal Recessive:

40
Eye, Brain

Publications for Parkinson Disease 14, Autosomal Recessive

Articles related to Parkinson Disease 14, Autosomal Recessive:

(show all 32)
# Title Authors PMID Year
1
PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort. 6 57 61
21700586 2011
2
Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism. 6 61 57
20938027 2010
3
Clinical and genetic delineation of neurodegeneration with brain iron accumulation. 57 6
18981035 2009
4
Characterization of PLA2G6 as a locus for dystonia-parkinsonism. 6 57
18570303 2009
5
A course-based undergraduate research experience examining neurodegeneration in Drosophila melanogaster teaches students to think, communicate, and perform like scientists. 61
32282825 2020
6
Lack of Association Between PLA2G6 Genetic Variation and Parkinson's Disease: A Systematic Review. 61
32801710 2020
7
Generation of induced pluripotent stem cells from a young-onset Parkinson's disease patient carrying the compound heterozygous PLA2G6 p.D331Y/p.M358IfsX mutations. 61
31493761 2019
8
Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling. 61
31548400 2019
9
PARK14 (D331Y) PLA2G6 Causes Early-Onset Degeneration of Substantia Nigra Dopaminergic Neurons by Inducing Mitochondrial Dysfunction, ER Stress, Mitophagy Impairment and Transcriptional Dysregulation in a Knockin Mouse Model. 61
30088174 2019
10
PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia. 61
30302010 2019
11
Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. 61
29909971 2018
12
Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease. 61
30042723 2018
13
PARK14 PLA2G6 mutants are defective in preventing rotenone-induced mitochondrial dysfunction, ROS generation and activation of mitochondrial apoptotic pathway. 61
29108286 2017
14
A new PLA2G6 mutation in a family with infantile neuroaxonal dystrophy. 61
28991683 2017
15
Alteration of mitochondrial protein PDHA1 in Lewy body disease and PARK14. 61
28564592 2017
16
Neuropathology of PARK14 is identical to idiopathic Parkinson's disease. 61
28211602 2017
17
Expanded phenotype and hippocampal involvement in a novel compound heterozygosity of adult PLA2G6 associated neurodegeneration (PARK14). 61
28094106 2017
18
Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism. 61
27942883 2017
19
PLA2G6 accumulates in Lewy bodies in PARK14 and idiopathic Parkinson's disease. 61
28213071 2017
20
Early Ataxia and Subsequent Parkinsonism: PLA2G6 Mutations Cause a Continuum Rather Than Three Discrete Phenotypes. 61
30868093 2017
21
Progressive Axonal Degeneration of Nigrostriatal Dopaminergic Neurons in Calcium-Independent Phospholipase A2β Knockout Mice. 61
27078024 2016
22
Impairment of PARK14-dependent Ca(2+) signalling is a novel determinant of Parkinson's disease. 61
26755131 2016
23
Neuroaxonal dystrophy in PLA2G6 knockout mice. 61
25950622 2015
24
Four novel rare mutations of PLA2G6 in Chinese population with Parkinson's disease. 61
23182313 2013
25
Analysis of PLA2G6 gene mutation in sporadic early-onset parkinsonism patients from Chinese population. 61
22406380 2012
26
PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson's disease. 61
22213678 2012
27
Autosomal recessive parkinsonism. 61
22166450 2012
28
PLA2G6 variant in Parkinson's disease. 61
21368765 2011
29
Rare causes of dystonia parkinsonism. 61
20694531 2010
30
Emerging parkinsonian phenotypes. 61
20817231 2010
31
Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. 61
20669327 2010
32
Hereditary parkinsonism: Parkinson disease look-alikes--an algorithm for clinicians to "PARK" genes and beyond. 61
19735092 2009

Variations for Parkinson Disease 14, Autosomal Recessive

ClinVar genetic disease variations for Parkinson Disease 14, Autosomal Recessive:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLA2G6 NM_003560.4(PLA2G6):c.2239C>T (p.Arg747Trp) SNV Pathogenic 6204 rs121908687 22:38508548-38508548 22:38112541-38112541
2 PLA2G6 NM_003560.4(PLA2G6):c.1904G>A (p.Arg635Gln) SNV Pathogenic 30366 rs387906863 22:38511664-38511664 22:38115657-38115657
3 PLA2G6 NM_003560.4(PLA2G6):c.1354C>T (p.Gln452Ter) SNV Pathogenic 30367 rs387906864 22:38522451-38522451 22:38126444-38126444
4 PLA2G6 NM_003560.4(PLA2G6):c.216C>A (p.Phe72Leu) SNV Pathogenic 30368 rs774631197 22:38541654-38541654 22:38145647-38145647
5 PLA2G6 NM_003560.4(PLA2G6):c.991G>T (p.Asp331Tyr) SNV Pathogenic 30371 rs199935023 22:38528924-38528924 22:38132917-38132917
6 PLA2G6 NM_003560.4(PLA2G6):c.2370T>G (p.Tyr790Ter) SNV Pathogenic 6195 rs121908680 22:38508219-38508219 22:38112212-38112212
7 PLA2G6 NM_003560.4(PLA2G6):c.2222G>A (p.Arg741Gln) SNV Likely pathogenic 6203 rs121908686 22:38508565-38508565 22:38112558-38112558
8 PLA2G6 NM_003560.4(PLA2G6):c.1427+1G>A SNV Likely pathogenic 437465 rs750939090 22:38522377-38522377 22:38126370-38126370
9 PLA2G6 NM_003560.4(PLA2G6):c.2239C>T (p.Arg747Trp) SNV Likely pathogenic 6204 rs121908687 22:38508548-38508548 22:38112541-38112541
10 PLA2G6 NM_003560.4(PLA2G6):c.238G>A (p.Ala80Thr) SNV Uncertain significance 6202 rs121908685 22:38541632-38541632 22:38145625-38145625
11 PLA2G6 NM_003560.4(PLA2G6):c.16C>T (p.Arg6Cys) SNV Uncertain significance 493345 rs143250889 22:38565418-38565418 22:38169411-38169411
12 PLA2G6 NM_003560.4(PLA2G6):c.1615G>A (p.Gly539Ser) SNV Uncertain significance 159740 rs143826762 22:38516893-38516893 22:38120886-38120886
13 PLA2G6 NM_003560.4(PLA2G6):c.898G>A (p.Ala300Thr) SNV Uncertain significance 235257 rs528966598 22:38529017-38529017 22:38133010-38133010
14 PLA2G6 NM_003560.4(PLA2G6):c.416G>A (p.Arg139His) SNV Uncertain significance 426191 rs141825182 22:38541454-38541454 22:38145447-38145447
15 PLA2G6 NM_003560.4(PLA2G6):c.101C>T (p.Ser34Leu) SNV Uncertain significance 341649 rs147948449 22:38565333-38565333 22:38169326-38169326
16 PLA2G6 NM_003560.4(PLA2G6):c.91G>A (p.Asp31Asn) SNV Uncertain significance 341650 rs150024227 22:38565343-38565343 22:38169336-38169336

UniProtKB/Swiss-Prot genetic disease variations for Parkinson Disease 14, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 PLA2G6 p.Arg741Gln VAR_062530 rs121908686
2 PLA2G6 p.Arg747Trp VAR_062531 rs121908687

Expression for Parkinson Disease 14, Autosomal Recessive

Search GEO for disease gene expression data for Parkinson Disease 14, Autosomal Recessive.

Pathways for Parkinson Disease 14, Autosomal Recessive

Pathways related to Parkinson Disease 14, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.79 VIPR1 CRH

GO Terms for Parkinson Disease 14, Autosomal Recessive

Cellular components related to Parkinson Disease 14, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 8.62 VIPR1 NR1H4

Biological processes related to Parkinson Disease 14, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of protein phosphorylation GO:0001934 9.16 PLA2G6 CRH
2 response to endoplasmic reticulum stress GO:0034976 8.96 PLA2G6 P4HB
3 positive regulation of insulin secretion involved in cellular response to glucose stimulus GO:0035774 8.8 PLA2G6 NR1H4 CRH

Sources for Parkinson Disease 14, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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