Details of Disease

General Information of Disease (ID: DISSE0H0)

• Disease Name: facioscapulohumeral muscular dystrophy
• Synonyms: muscular dystrophy, Landouzy-Dejerine; facioscapulohumeral myopathy; facioscapulohumeral muscular dystrophy; facioscapulohumeral dystrophy; Landouzy-Dejerine myopathy; Landouzy-Dejerine muscular dystrophy; Landouzy Dejerine muscular dystrophy; FSHD; FSH dystrophy
• Disease Class: 8C70: Muscular dystrophy
• Definition: An autosomal dominant disorder affecting the skeletal muscles of the face, scapula, and upper arm. Patients present with muscle weakness in these anatomic areas. The muscle weakness eventually spreads to other skeletal muscles as well.
• Disease Hierarchy:
  DISV66YX: Progressive muscular dystrophy
  DISLXQHV: Telomere syndrome
  DISSE0H0: facioscapulohumeral muscular dystrophy
• ICD Code: ICD-11: ICD-11: 8C70
• Disease Identifiers:
  MONDO ID: MONDO_0001347
  MESH ID: D020391
  UMLS CUI: C0238288
  MedGen ID: 65956
  Orphanet ID: 269
  SNOMED CT ID: 399091004

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
RG6237	DM6GJTS	Phase 2	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDKN1A	TT9GUW0	Strong	Biomarker	[2]
DCN	TTB3XAN	Strong	Biomarker	[2]
DMD	TTWLFXU	Strong	Biomarker	[3]
FAT1	TTGUJYV	Strong	Biomarker	[4]
FLNA	TTSTRZY	Strong	Genetic Variation	[5]
G3BP1	TTG0R8Z	Strong	Biomarker	[6]
ITGB6	TTKQSXZ	Strong	Biomarker	[7]
MYH7	TTNIMDP	Strong	Genetic Variation	[8]
RTN4	TT7GXMU	Strong	Biomarker	[9]
SLC38A2	TTUSC27	Strong	Genetic Variation	[10]
TACR2	TTYO0A3	Strong	Biomarker	[11]

This Disease Is Related to 35 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ASH1L	OTUT5NLJ	Limited	Biomarker	[12]
CCNA1	OTX4HD45	Limited	Altered Expression	[13]
CDC27	OTDT45XJ	Limited	Genetic Variation	[14]
CHAF1B	OTOMK4KH	Limited	Altered Expression	[15]
CNOT7	OTJBKCPI	Limited	Altered Expression	[15]
CNOT8	OT6CMCS0	Limited	Altered Expression	[15]
CRYM	OTRGSR6B	Limited	Altered Expression	[16]
LRP2BP	OTVEH7V5	Limited	Altered Expression	[17]
MBD3L1	OTQCIJ4U	Limited	Altered Expression	[15]
MYF5	OTTVO2S5	Limited	Altered Expression	[18]
PSD4	OTEFB87Z	Limited	Biomarker	[19]
RBFOX1	OTFPKEL7	Limited	Altered Expression	[20]
SKP1	OT5BPAZ4	Limited	Altered Expression	[21]
SUMF2	OT37I8JL	Limited	Biomarker	[22]
SMCHD1	OTBV52DR	Supportive	Autosomal dominant	[23]
SAT2	OT28QL7H	moderate	Genetic Variation	[10]
ACAN	OTUOCW8K	Strong	Biomarker	[2]
ANXA13	OTM33P73	Strong	Biomarker	[24]
CAPN3	OTCHG3YK	Strong	Genetic Variation	[20]
COL3A1	OTT1EMLM	Strong	Biomarker	[2]
CTCF	OT8ZB70U	Strong	Biomarker	[25]
DCTN3	OTQOSUES	Strong	Biomarker	[26]
EIF3K	OTGTKVGO	Strong	Altered Expression	[27]
ELN	OTFSO7PG	Strong	Biomarker	[2]
FRG2	OTKIK5HR	Strong	Altered Expression	[28]
GSTT2	OTANW3TJ	Strong	Biomarker	[2]
HSPA4	OT5HR0AR	Strong	Biomarker	[2]
LUM	OTSRC874	Strong	Biomarker	[2]
PAX7	OTDMQRPO	Strong	Biomarker	[29]
PCNT	OTW4Z65J	Strong	Genetic Variation	[30]
PDLIM3	OTVXQC81	Strong	Altered Expression	[31]
PITX1	OTA0UN4C	Strong	Biomarker	[32]
RTN1	OTCX1SMK	Strong	Biomarker	[9]
SPECC1	OTPEML48	Strong	Biomarker	[9]
FXR1	OTEMQ1SR	Definitive	Altered Expression	[33]

References

• [1] Clinical pipeline report, company report or official report of Roche
• [2] Facioscapulohumeral muscular dystrophy (FSHD) myoblasts demonstrate increased susceptibility to oxidative stress.Neuromuscul Disord. 2003 May;13(4):322-33. doi: 10.1016/s0960-8966(02)00284-5.
• [3] Value of muscle enzyme measurement in evaluating different neuromuscular diseases.Clin Chim Acta. 2012 Feb 18;413(3-4):520-4. doi: 10.1016/j.cca.2011.11.016. Epub 2011 Nov 25.
• [4] FAT1 Gene Alteration in Facioscapulohumeral Muscular Dystrophy Type 1.Yonsei Med J. 2018 Mar;59(2):337-340. doi: 10.3349/ymj.2018.59.2.337.
• [5] Whole genome sequencing and 6-year follow-up of a mother and daughter with frontometaphyseal dysplasia associated with keratitis, xerosis, poikiloderma, and acro-osteolysis: A case report.Medicine (Baltimore). 2018 Jul;97(28):e11283. doi: 10.1097/MD.0000000000011283.
• [6] Foot-and-Mouth Disease Virus Counteracts on Internal Ribosome Entry Site Suppression by G3BP1 and Inhibits G3BP1-Mediated Stress Granule Assembly via Post-Translational Mechanisms.Front Immunol. 2018 May 25;9:1142. doi: 10.3389/fimmu.2018.01142. eCollection 2018.
• [7] Inhibition of viral replication by small interfering RNA targeting of the foot-and-mouth disease virus receptor integrin 6.Exp Ther Med. 2017 Jul;14(1):735-742. doi: 10.3892/etm.2017.4560. Epub 2017 Jun 7.
• [8] Is deltoid muscle biopsy useful in isolated camptocormia? A prospective study.Eur J Neurol. 2016 Jun;23(6):1086-92. doi: 10.1111/ene.12989. Epub 2016 Mar 10.
• [9] Development and validation of a foot-and-mouth disease virus SAT serotype-specific 3ABC assay to differentiate infected from vaccinated animals.J Virol Methods. 2018 May;255:44-51. doi: 10.1016/j.jviromet.2018.02.006. Epub 2018 Feb 8.
• [10] Generation of monoclonal antibodies against foot-and-mouth disease virus SAT 2 and the development of a lateral flow strip test for virus detection.Transbound Emerg Dis. 2019 May;66(3):1158-1166. doi: 10.1111/tbed.13076. Epub 2018 Dec 10.
• [11] Improved foot-and-mouth disease vaccine with O PanAsia-2 strain protect pigs against O/Jincheon/SKR/2014 originated from South Korea.Vaccine. 2020 Jan 29;38(5):1120-1128. doi: 10.1016/j.vaccine.2019.11.029. Epub 2019 Dec 3.
• [12] A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy.Cell. 2012 May 11;149(4):819-31. doi: 10.1016/j.cell.2012.03.035. Epub 2012 Apr 26.
• [13] Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1).PLoS One. 2013 Sep 3;8(9):e73573. doi: 10.1371/journal.pone.0073573. eCollection 2013.
• [14] Whole-exome sequencing identifies unique mutations and copy number losses in calcifying fibrous tumor of the pleura: report of 3 cases and review of the literature.Hum Pathol. 2018 Aug;78:36-43. doi: 10.1016/j.humpath.2018.04.005. Epub 2018 Apr 22.
• [15] NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins.Elife. 2018 Mar 13;7:e31023. doi: 10.7554/eLife.31023.
• [16] Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy.Exp Neurol. 2007 Jun;205(2):583-6. doi: 10.1016/j.expneurol.2007.03.009. Epub 2007 Mar 21.
• [17] Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy.Neurology. 2007 Feb 20;68(8):569-77. doi: 10.1212/01.wnl.0000251269.31442.d9. Epub 2006 Dec 6.
• [18] DUX4c is up-regulated in FSHD. It induces the MYF5 protein and human myoblast proliferation.PLoS One. 2009 Oct 15;4(10):e7482. doi: 10.1371/journal.pone.0007482.
• [19] AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD.JCI Insight. 2018 Nov 15;3(22):e123538. doi: 10.1172/jci.insight.123538.
• [20] Rbfox1 downregulation and altered calpain 3 splicing by FRG1 in a mouse model of Facioscapulohumeral muscular dystrophy (FSHD).PLoS Genet. 2013;9(1):e1003186. doi: 10.1371/journal.pgen.1003186. Epub 2013 Jan 3.
• [21] Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation.Biochem Biophys Res Commun. 2009 Nov 13;389(2):279-83. doi: 10.1016/j.bbrc.2009.08.133. Epub 2009 Aug 28.
• [22] A new dosage test for subtelomeric 4;10 translocations improves conventional diagnosis of facioscapulohumeral muscular dystrophy (FSHD).J Med Genet. 1999 Nov;36(11):823-8.
• [23] Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet. 2012 Dec;44(12):1370-4. doi: 10.1038/ng.2454. Epub 2012 Nov 11.
• [24] Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant.Vaccines (Basel). 2019 Oct 9;7(4):143. doi: 10.3390/vaccines7040143.
• [25] D4Z4 as a prototype of CTCF and lamins-dependent insulator in human cells.Nucleus. 2010 Jan-Feb;1(1):30-6. doi: 10.4161/nucl.1.1.10799.
• [26] Interaction of foot-and-mouth disease virus nonstructural protein 3A with host protein DCTN3 is important for viral virulence in cattle.J Virol. 2014 Mar;88(5):2737-47. doi: 10.1128/JVI.03059-13. Epub 2013 Dec 18.
• [27] Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients.J Med Genet. 2008 Oct;45(10):679-85. doi: 10.1136/jmg.2008.060541. Epub 2008 Jul 15.
• [28] The Krppel-like factor 15 as a molecular link between myogenic factors and a chromosome 4q transcriptional enhancer implicated in facioscapulohumeral dystrophy.J Biol Chem. 2011 Dec 30;286(52):44620-31. doi: 10.1074/jbc.M111.254052. Epub 2011 Sep 21.
• [29] PAX7 target gene repression is a superior FSHD biomarker than DUX4 target gene activation, associating with pathological severity and identifying FSHD at the single-cell level.Hum Mol Genet. 2019 Jul 1;28(13):2224-2236. doi: 10.1093/hmg/ddz043.
• [30] Genetic and antigenic characterization of serotype O FMD viruses from East Africa for the selection of suitable vaccine strain.Vaccine. 2017 Dec 14;35(49 Pt B):6842-6849. doi: 10.1016/j.vaccine.2017.10.040.
• [31] Actinin-associated LIM protein-deficient mice maintain normal development and structure of skeletal muscle.Mol Cell Biol. 2001 Mar;21(5):1682-7. doi: 10.1128/MCB.21.5.1682-1687.2001.
• [32] Testing the effects of FSHD candidate gene expression in vertebrate muscle development.Int J Clin Exp Pathol. 2010 Mar 28;3(4):386-400.
• [33] A novel role for the RNA-binding protein FXR1P in myoblasts cell-cycle progression by modulating p21/Cdkn1a/Cip1/Waf1 mRNA stability.PLoS Genet. 2013 Mar;9(3):e1003367. doi: 10.1371/journal.pgen.1003367. Epub 2013 Mar 21.