Details of Disease

General Information of Disease (ID: DISF24LW)

• Disease Name: Myofibrillar myopathy
• Synonyms: desmin related myopathy (former name); desmin storage myopathy (former name); Protein surplus myopathy (former name); Desminopathy (type); Zaspopathy (type); myofibrillar myopathies; myotilinopathy (type); filaminopathy (type); Alpha Beta crystallinopathy (type); myofibrillar myopathy (disease); myofibrillar myopathy
• Definition: Myofibrillar myopathy (MFM) describes a group of skeletal and cardiac muscle disorders, defined by the disintegration of myofibrils and aggregation of degradation products into intracellular inclusions, and is typically clinically characterized by slowly-progressive muscle weakness, which initially involves the distal muscles, but is highly variable and that can affect the proximal muscles as well as the cardiac and respiratory muscles in some patients.
• Disease Hierarchy:
  DISZ9JP4: Congenital structural myopathy
  DISF24LW: Myofibrillar myopathy
• Disease Identifiers:
  MONDO ID: MONDO_0018943
  MESH ID: C580316
  UMLS CUI: C2678065
  MedGen ID: 395532
  HPO ID: HP:0003715
  Orphanet ID: 593
  SNOMED CT ID: 699269005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CPT1B	TTDL0NY	Strong	Biomarker	[1]
CRYAB	TT7RUHB	Strong	Biomarker	[2]
CS	TTZA6B3	Strong	Biomarker	[3]
FHL1	TTI7ENL	Strong	Genetic Variation	[4]
HSPB8	TTY0OJN	Strong	Biomarker	[5]
MYH7	TTNIMDP	Strong	Genetic Variation	[6]
PLN	TTMCVJF	Strong	Biomarker	[7]
TARDBP	TT9RZ03	Strong	Biomarker	[5]
TTR	TTPOYU7	Strong	CausalMutation	[8]
USH2A	TTVCLLA	Strong	Genetic Variation	[1]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC24A1	DTJZ7M5	Strong	Biomarker	[1]
SLC7A10	DTVL2JY	Strong	Biomarker	[1]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MATR3	OTESJ5S7	Limited	Biomarker	[9]
PDLIM5	OTLQVV22	Limited	Genetic Variation	[4]
PYROXD1	OTPGO23E	Limited	Genetic Variation	[10]
DES	OTI09KBW	moderate	Genetic Variation	[11]
ACTC1	OTJU04B1	Strong	Genetic Variation	[1]
ATP2A1	OT959A3A	Strong	Biomarker	[7]
CAPN3	OTCHG3YK	Strong	Genetic Variation	[12]
CFL2	OTE2W0DH	Strong	Genetic Variation	[13]
DNAJB6	OTMHIIAN	Strong	Biomarker	[14]
FLNC	OT3F8J6Y	Strong	Genetic Variation	[15]
LDB3	OTGQL1AM	Strong	Genetic Variation	[16]
MYOT	OTCEW5XW	Strong	Genetic Variation	[17]
NRAP	OTO6H3YF	Strong	Genetic Variation	[4]
PSME1	OTDHLJWH	Strong	Biomarker	[18]
TPM2	OTA1L0P8	Strong	Biomarker	[1]
TTN	OT0LZ058	Strong	Genetic Variation	[19]
ACTA1	OTOVGLPG	Definitive	Genetic Variation	[20]
BAG3	OTVXYUDQ	Definitive	Autosomal dominant	[21]

References

• [1] Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways.Physiol Genomics. 2018 Dec 1;50(12):1036-1050. doi: 10.1152/physiolgenomics.00044.2018. Epub 2018 Oct 5.
• [2] The early response of B-crystallin to a single bout of aerobic exercise in mouse skeletal muscles depends upon fiber oxidative features.Redox Biol. 2019 Jun;24:101183. doi: 10.1016/j.redox.2019.101183. Epub 2019 Apr 3.
• [3] Mitochondrial abnormalities in myofibrillar myopathies.Clin Neuropathol. 2014 Mar-Apr;33(2):134-42. doi: 10.5414/NP300693.
• [4] Exome sequencing identifies variants in two genes encoding the LIM-proteins NRAP and FHL1 in an Italian patient with BAG3 myofibrillar myopathy.J Muscle Res Cell Motil. 2016 Jun;37(3):101-15. doi: 10.1007/s10974-016-9451-7. Epub 2016 Jul 21.
• [5] Altered TDP-43-dependent splicing in HSPB8-related distal hereditary motor neuropathy and myofibrillar myopathy.Eur J Neurol. 2018 Jan;25(1):154-163. doi: 10.1111/ene.13478. Epub 2017 Dec 2.
• [6] 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.
• [7] Skeletal muscle sarcoplasmic reticulum phenotype in myotonic dystrophy.Neuromuscul Disord. 1996 Jan;6(1):33-47. doi: 10.1016/0960-8966(95)00016-x.
• [8] Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):E6428-E6436. doi: 10.1073/pnas.1802977115. Epub 2018 Jun 25.
• [9] Autosomal-dominant distal myopathy associated with a recurrent missense mutation in the gene encoding the nuclear matrix protein, matrin 3. Am J Hum Genet. 2009 Apr;84(4):511-8. doi: 10.1016/j.ajhg.2009.03.006. Epub 2009 Apr 2.
• [10] Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy.J Neurol. 2019 Feb;266(2):353-360. doi: 10.1007/s00415-018-9137-8. Epub 2018 Dec 4.
• [11] Recessive DES cardio/myopathy without myofibrillar aggregates: intronic splice variant silences one allele leaving only missense L190P-desmin.Eur J Hum Genet. 2019 Aug;27(8):1267-1273. doi: 10.1038/s41431-019-0393-6. Epub 2019 Apr 25.
• [12] Translocation of molecular chaperones to the titin springs is common in skeletal myopathy patients and affects sarcomere function.Acta Neuropathol Commun. 2017 Sep 15;5(1):72. doi: 10.1186/s40478-017-0474-0.
• [13] Congenital myopathy caused by a novel missense mutation in the CFL2 gene.Neuromuscul Disord. 2012 Jul;22(7):632-9. doi: 10.1016/j.nmd.2012.03.008. Epub 2012 May 4.
• [14] Diagnostically important muscle pathology in DNAJB6 mutated LGMD1D.Acta Neuropathol Commun. 2016 Feb 5;4:9. doi: 10.1186/s40478-016-0276-9.
• [15] A novel mutation in the N-terminal acting-binding domain of Filamin C protein causing a distal myofibrillar myopathy.J Neurol Sci. 2019 Mar 15;398:75-78. doi: 10.1016/j.jns.2019.01.019. Epub 2019 Jan 17.
• [16] Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes.BMC Genomics. 2013 Apr 15;14:248. doi: 10.1186/1471-2164-14-248.
• [17] Novel recessive myotilin mutation causes severe myofibrillar myopathy.Neurogenetics. 2014 Aug;15(3):151-6. doi: 10.1007/s10048-014-0410-4. Epub 2014 Jun 14.
• [18] Proteasomal expression, induction of immunoproteasome subunits, and local MHC class I presentation in myofibrillar myopathy and inclusion body myositis.J Neuropathol Exp Neurol. 2004 May;63(5):484-98. doi: 10.1093/jnen/63.5.484.
• [19] Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy.Clin Genet. 2017 Dec;92(6):616-623. doi: 10.1111/cge.13043. Epub 2017 May 18.
• [20] New aspects of myofibrillar myopathies.Curr Opin Neurol. 2016 Oct;29(5):628-34. doi: 10.1097/WCO.0000000000000357.
• [21] 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.