Details of Disease

General Information of Disease (ID: DIS83JHH)

• Disease Name: Lafora disease
• Synonyms: epilepsy progressive myoclonic 2; Lafora body disease; Epm2; Melf; Lafora body disorder; epilepsy, progressive myoclonic, 2B; epilepsy, progressive myoclonic, 2A; Lafora progressive myoclonic epilepsy; progressive myoclonus epilepsy type 2; epilepsy, progressive myoclonic 2A (Lafora); progressive myoclonic epilepsy type 2; epilepsy, progressive myoclonic 2B (Lafora); EPM2; myoclonic epilepsy of Lafora; Lafora disease; PME type 2; Lafora's disease
• Definition: Lafora disease (LD) is a rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus and/or generalized seizures, visual hallucinations (partial occipital seizures), and progressive neurological decline.
• Disease Hierarchy:
  DISYGNOB: Disorder of glycogen metabolism
  DISAMCNS: Progressive myoclonus epilepsy
  DISOJJ2D: Movement disorder
  DIS83JHH: Lafora disease
• Disease Identifiers:
  MONDO ID: MONDO_0009697
  MESH ID: D020192
  UMLS CUI: C0751783
  OMIM ID: 254780
  MedGen ID: 155631
  Orphanet ID: 501
  SNOMED CT ID: 230425004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
LAMP1	TTC214J	Limited	Biomarker	[1]
LAMP2	TTULDG7	Limited	Biomarker	[1]
AMY2A	TTCGSZ4	Strong	Biomarker	[2]
BCKDK	TT7WD2Q	Strong	Genetic Variation	[3]
CLN3	TTORF9W	Strong	Genetic Variation	[4]
GBA	TT1B5PU	Strong	Altered Expression	[5]
GRK5	TTTCXO0	Strong	Biomarker	[6]
TPP1	TTOVYPT	Strong	Genetic Variation	[4]

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EPM2AIP1	OT21ALNF	Limited	Biomarker	[7]
OPN1MW	OTPJ7LX4	Limited	Biomarker	[8]
SNCB	OTELSEK6	Limited	Altered Expression	[9]
ATP13A2	OTKWBUGK	Strong	Altered Expression	[10]
BCL2L13	OT2VRFTM	Strong	Altered Expression	[11]
CHCHD2	OTL5PA3Y	Strong	Genetic Variation	[12]
CLN5	OTY265P6	Strong	Genetic Variation	[4]
CSTB	OT3U0JF8	Strong	Biomarker	[13]
DCP1A	OT3NCON3	Strong	Altered Expression	[14]
DNAJC13	OTYAVVJ6	Strong	Genetic Variation	[15]
GYG1	OT9PU6I2	Strong	Biomarker	[16]
LMTK2	OT93MVIC	Strong	Biomarker	[17]
MAP1LC3A	OTPMGIU4	Strong	Biomarker	[1]
NBL1	OTT37U4O	Strong	Biomarker	[18]
NFU1	OTL58QZS	Strong	Biomarker	[19]
NNAT	OTNRLO7G	Strong	Biomarker	[20]
PARN	OTTG4PE3	Strong	Biomarker	[18]
PPP1R3B	OTVCRXEZ	Strong	Genetic Variation	[21]
PPP1R3C	OTEU05TX	Strong	Genetic Variation	[21]
SERPINI1	OTUJHIJW	Strong	Biomarker	[22]
STX1B	OTSW59X0	Strong	Genetic Variation	[3]
TRIM32	OTJOV0PG	Strong	Biomarker	[23]
CBLL2	OTB4AD3V	Definitive	Biomarker	[24]
EPM2A	OTJU4IAG	Definitive	Autosomal recessive	[25]
MUL1	OT2JC9YR	Definitive	Biomarker	[24]
NHLRC1	OTRQ0A4W	Definitive	Autosomal recessive	[25]
PFKL	OTVHGAT7	Definitive	Genetic Variation	[26]
PRKN	OTJBN41W	Definitive	Biomarker	[24]

References

• [1] Lysosomes, autophagosomes and Alzheimer pathology in dementia with Lewy body disease.Neuropathology. 2018 May 10. doi: 10.1111/neup.12472. Online ahead of print.
• [2] Central Nervous System Delivery and Biodistribution Analysis of an Antibody-Enzyme Fusion for the Treatment of Lafora Disease.Mol Pharm. 2019 Sep 3;16(9):3791-3801. doi: 10.1021/acs.molpharmaceut.9b00396. Epub 2019 Aug 2.
• [3] Parkinson's disease susceptibility variants and severity of Lewy body pathology.Parkinsonism Relat Disord. 2017 Nov;44:79-84. doi: 10.1016/j.parkreldis.2017.09.009. Epub 2017 Sep 11.
• [4] Advances in the genetics of progressive myoclonus epilepsy.Am J Med Genet. 2001 Summer;106(2):129-38. doi: 10.1002/ajmg.1575.
• [5] Age-related neurochemical and behavioural changes in D409V/WT GBA1 mouse: Relevance to lewy body dementia.Neurochem Int. 2019 Oct;129:104502. doi: 10.1016/j.neuint.2019.104502. Epub 2019 Jul 9.
• [6] Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles.J Neuropathol Exp Neurol. 2006 Dec;65(12):1157-69. doi: 10.1097/01.jnen.0000248542.82681.12.
• [7] Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy.Hum Mol Genet. 2004 Jun 1;13(11):1117-29. doi: 10.1093/hmg/ddh130. Epub 2004 Apr 21.
• [8] Corticobasal syndrome with visual hallucinations and probable REM-sleep behavior disorder: an autopsied case report of a patient with CBD and LBD pathology.Neurocase. 2019 Feb-Apr;25(1-2):26-33. doi: 10.1080/13554794.2019.1604973. Epub 2019 Apr 22.
• [9] Accumulation of beta-synuclein in cortical neurons is associated with autophagy attenuation in the brains of dementia with Lewy body patients.Brain Res. 2018 Feb 15;1681:1-13. doi: 10.1016/j.brainres.2017.12.026. Epub 2017 Dec 24.
• [10] Glucocerebrosidase mutations alter the endoplasmic reticulum and lysosomes in Lewy body disease.J Neurochem. 2012 Oct;123(2):298-309. doi: 10.1111/j.1471-4159.2012.07879.x. Epub 2012 Aug 22.
• [11] Degradation of altered mitochondria by autophagy is impaired in Lafora disease.FEBS J. 2018 Jun;285(11):2071-2090. doi: 10.1111/febs.14468. Epub 2018 Apr 23.
• [12] Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders.Neurology. 2015 Dec 8;85(23):2016-25. doi: 10.1212/WNL.0000000000002170. Epub 2015 Nov 11.
• [13] Debate: Does genetic information in humans help us treat patients PRO--genetic information in humans helps us treat patients. CON--genetic information does not help at all. Epilepsia. 2008 Dec;49 Suppl 9:13-24.
• [14] Lafora disease E3 ubiquitin ligase malin is recruited to the processing bodies and regulates the microRNA-mediated gene silencing process via the decapping enzyme Dcp1a.RNA Biol. 2012 Dec;9(12):1440-9. doi: 10.4161/rna.22708. Epub 2012 Nov 6.
• [15] DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients.Eur J Neurol. 2015 Sep;22(9):1323-5. doi: 10.1111/ene.12770.
• [16] Glycogen and its metabolism: some new developments and old themes.Biochem J. 2012 Feb 1;441(3):763-87. doi: 10.1042/BJ20111416.
• [17] Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease.Sci Rep. 2019 Nov 20;9(1):17222. doi: 10.1038/s41598-019-53638-9.
• [18] Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease.Cortex. 2017 Jul;92:8-18. doi: 10.1016/j.cortex.2017.02.016. Epub 2017 Mar 18.
• [19] The Lafora disease gene product laforin interacts with HIRIP5, a phylogenetically conserved protein containing a NifU-like domain.Hum Mol Genet. 2003 Sep 15;12(18):2359-68. doi: 10.1093/hmg/ddg253. Epub 2003 Jul 29.
• [20] Neuronatin gene: Imprinted and misfolded: Studies in Lafora disease, diabetes and cancer may implicate NNAT-aggregates as a common downstream participant in neuronal loss.Genomics. 2014 Feb-Mar;103(2-3):183-8. doi: 10.1016/j.ygeno.2013.12.001. Epub 2013 Dec 15.
• [21] A PTG variant contributes to a milder phenotype in Lafora disease.PLoS One. 2011;6(6):e21294. doi: 10.1371/journal.pone.0021294. Epub 2011 Jun 30.
• [22] Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA.Acta Neuropathol Commun. 2018 Jul 26;6(1):68. doi: 10.1186/s40478-018-0573-6.
• [23] Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level.BMC Evol Biol. 2011 Jul 28;11:225. doi: 10.1186/1471-2148-11-225.
• [24] Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease.Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118613. doi: 10.1016/j.bbamcr.2019.118613. Epub 2019 Nov 21.
• [25] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [26] Lafora disease is not linked to the Unverricht-Lundborg locus.Am J Med Genet. 1995 Feb 27;60(1):80-4. doi: 10.1002/ajmg.1320600114.