Details of Disease

General Information of Disease (ID: DIS05LFS)

• Disease Name: Young-onset Parkinson disease
• Synonyms: early-onset Parkinson's disease; early-onset Parkinson disease; YOPD
• Definition: A form of Parkinson disease (PD) characterized by an age of onset between 21-45 years, rigidity, painful cramps followed by tremor, bradykinesia, dystonia, gait complaints and falls, and other non-motor symptoms. A slow disease progression and a more pronounced response to dopaminergic therapy are also observed in most YOPD forms.
• Disease Hierarchy:
  DISQVHKL: Parkinson disease
  DIS05LFS: Young-onset Parkinson disease
• Disease Identifiers:
  MONDO ID: MONDO_0017279
  UMLS CUI: C4275179
  MedGen ID: 907947
  Orphanet ID: 2828
  SNOMED CT ID: 715345007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
VPS13C	OT5GHC9K	Supportive	Autosomal recessive	[1]
BAG5	OT0J97C6	Limited	Biomarker	[8]
C1orf52	OT8RQW3W	Limited	Biomarker	[8]
DGCR8	OT62LXE4	Limited	Biomarker	[5]
EN2	OT7EZCM2	Limited	Genetic Variation	[9]
HS1BP3	OT5NSZJ1	Limited	Genetic Variation	[10]
LGALS4	OTKQCG0H	Limited	Biomarker	[11]
LRRC4	OT7XJ70N	Limited	Biomarker	[8]
MCU	OTQZAYWQ	Limited	Biomarker	[12]
MICU1	OTS7N0LE	Limited	Biomarker	[13]
MICU2	OTZY0PM2	Limited	Genetic Variation	[13]
NIF3L1	OT4MP90J	Limited	Genetic Variation	[14]
OMA1	OT0JRVY7	Limited	Biomarker	[15]
PITX3	OTE2KT8P	Limited	Genetic Variation	[16]
SNCB	OTELSEK6	Limited	Altered Expression	[17]
TMEM230	OTAFALFV	Limited	Genetic Variation	[18]
DNAJC6	OT1P6ZIE	Supportive	Autosomal recessive	[19]
PARK7	OT0SKNTG	Supportive	Autosomal recessive	[6]
PINK1	OT50NR57	Supportive	Autosomal recessive	[6]
PODXL	OTPNQXF3	Supportive	Autosomal recessive	[20]
PRKN	OTJBN41W	Supportive	Autosomal recessive	[6]
SYNJ1	OTTE02XC	Supportive	Autosomal recessive	[21]
ATP13A2	OTKWBUGK	Strong	Altered Expression	[22]
CBLL2	OTB4AD3V	Strong	Genetic Variation	[23]
FBXO7	OTGTN8TJ	Strong	Biomarker	[24]
MUL1	OT2JC9YR	Strong	Genetic Variation	[23]
PLA2G6	OT5FL0WU	Strong	Genetic Variation	[25]
RAB39B	OTDCLLT0	Strong	Genetic Variation	[26]

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CIT	TT3BKTU	Limited	Biomarker	[2]
TOR1A	TTF85KW	Limited	Genetic Variation	[3]
GCH1	TTLSWP6	Strong	Biomarker	[4]
LRRK2	TTK0FEA	Strong	Biomarker	[5]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PARK7	DEPOVCH	Supportive	Autosomal recessive	[6]
PARK7	DEPOVCH	Strong	Genetic Variation	[7]

References

• [1] Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. Am J Hum Genet. 2016 Mar 3;98(3):500-513. doi: 10.1016/j.ajhg.2016.01.014.
• [2] Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]beta-CIT SPECT analysis.Eur J Nucl Med Mol Imaging. 2006 Sep;33(9):1084-90. doi: 10.1007/s00259-006-0104-8. Epub 2006 May 13.
• [3] DYT1 mutations in early onset primary torsion dystonia and Parkinson disease patients in Chinese populations.Neurosci Lett. 2009 Jan 30;450(2):117-21. doi: 10.1016/j.neulet.2008.10.111. Epub 2008 Nov 20.
• [4] Dopa-responsive dystonia or early-onset Parkinson disease - Genotype-phenotype correlation.Neurol Neurochir Pol. 2017 Jan-Feb;51(1):1-6. doi: 10.1016/j.pjnns.2016.07.013. Epub 2016 Sep 12.
• [5] Association between early-onset Parkinson disease and 22q11.2 deletion syndrome: identification of a novel genetic form of Parkinson disease and its clinical implications.JAMA Neurol. 2013 Nov;70(11):1359-66. doi: 10.1001/jamaneurol.2013.3646.
• [6] Role of mendelian genes in "sporadic" Parkinson's disease. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S66-70. doi: 10.1016/S1353-8020(11)70022-0.
• [7] Familial early onset Parkinson's disease caused by a homozygous frameshift variant in PARK7: Clinical features and literature update.Parkinsonism Relat Disord. 2019 Jul;64:308-311. doi: 10.1016/j.parkreldis.2019.03.013. Epub 2019 Mar 22.
• [8] BAG5 inhibits parkin and enhances dopaminergic neuron degeneration.Neuron. 2004 Dec 16;44(6):931-45. doi: 10.1016/j.neuron.2004.11.026.
• [9] Haplotype analysis of the engrailed-2 gene in young-onset Parkinson's disease.Neurodegener Dis. 2009;6(3):102-5. doi: 10.1159/000207796. Epub 2009 Mar 6.
• [10] A family with Parkinson disease, essential tremor, bell palsy, and parkin mutations.Arch Neurol. 2007 Mar;64(3):421-4. doi: 10.1001/archneur.64.3.421.
• [11] Overexpression of Buffy enhances the loss of parkin and suppresses the loss of Pink1 phenotypes in Drosophila.Genome. 2017 Mar;60(3):241-247. doi: 10.1139/gen-2016-0165. Epub 2016 Dec 22.
• [12] Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1(-/-) zebrafish.Eur J Neurosci. 2017 Feb;45(4):528-535. doi: 10.1111/ejn.13473. Epub 2016 Dec 28.
• [13] Parkin-dependent regulation of the MCU complex component MICU1.Sci Rep. 2018 Sep 21;8(1):14199. doi: 10.1038/s41598-018-32551-7.
• [14] Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson's Disease.Eur J Neurol. 2006 Apr;13(4):385-90. doi: 10.1111/j.1468-1331.2006.01249.x.
• [15] Reciprocal Roles of Tom7 and OMA1 during Mitochondrial Import and Activation of PINK1.Mol Cell. 2019 Mar 7;73(5):1028-1043.e5. doi: 10.1016/j.molcel.2019.01.002. Epub 2019 Feb 4.
• [16] PITX3 polymorphism is associated with early onset Parkinson's disease.Neurobiol Aging. 2010 Jan;31(1):114-7. doi: 10.1016/j.neurobiolaging.2008.03.008. Epub 2008 Apr 16.
• [17] Alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease.Mov Disord. 1999 May;14(3):417-22. doi: 10.1002/1531-8257(199905)14:3<417::aid-mds1005>3.0.co;2-x.
• [18] Screening for TMEM230 mutations in young-onset Parkinson's disease.Neurobiol Aging. 2017 Oct;58:239.e9-239.e10. doi: 10.1016/j.neurobiolaging.2017.06.011. Epub 2017 Jun 24.
• [19] DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease. Ann Neurol. 2016 Feb;79(2):244-56. doi: 10.1002/ana.24553. Epub 2016 Jan 14.
• [20] Discovery of a frameshift mutation in podocalyxin-like (PODXL) gene, coding for a neural adhesion molecule, as causal for autosomal-recessive juvenile Parkinsonism. J Med Genet. 2016 Jul;53(7):450-6. doi: 10.1136/jmedgenet-2015-103459. Epub 2016 Feb 10.
• [21] Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism. Hum Mutat. 2013 Sep;34(9):1208-15. doi: 10.1002/humu.22373. Epub 2013 Aug 6.
• [22] Overlapping expression patterns and functions of three paralogous P5B ATPases in Caenorhabditis elegans.PLoS One. 2018 Mar 16;13(3):e0194451. doi: 10.1371/journal.pone.0194451. eCollection 2018.
• [23] The landscape of Parkin variants reveals pathogenic mechanisms and therapeutic targets in Parkinson's disease.Hum Mol Genet. 2019 Sep 1;28(17):2811-2825. doi: 10.1093/hmg/ddz080.
• [24] Genetic analysis of ATP13A2, PLA2G6 and FBXO7 in a cohort of Chinese patients with early-onset Parkinson's disease.Sci Rep. 2018 Sep 19;8(1):14028. doi: 10.1038/s41598-018-32217-4.
• [25] 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.Mol Neurobiol. 2019 Jun;56(6):3835-3853. doi: 10.1007/s12035-018-1118-5. Epub 2018 Aug 8.
• [26] Generation of RAB39B knockout isogenic human embryonic stem cell lines to model RAB39B-mediated Parkinson's disease.Stem Cell Res. 2018 Apr;28:161-164. doi: 10.1016/j.scr.2018.02.015. Epub 2018 Feb 21.