Details of Disease | DrugMAP

General Information of Disease (ID: DISK4S94)

Disease Name	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
Synonyms	inclusion body myopathy with early-onset Paget disease and frontotemporal dementia; pagetoid neuroskeletal syndrome; pagetoid amyotrophic lateral sclerosis; limb-girdle muscular dystrophy with Paget disease of bone; inclusion body myopathy/Paget disease/frontotemporal dementia; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia; inclusion body myopathy with Paget's disease of bone and frontotemporal dementia; IBMPFD
Definition	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative genetic disorder characterized by adult-onset proximal and distal muscle weakness (clinically resembling limb-girdle muscular dystrophy); early-onset Paget disease of bone, manifesting with bone pain, deformity and enlargement of the long-bones; and premature frontotemporal dementia, manifesting first with dysnomia, dyscalculia and comprehension deficits followed by progressive aphasia, alexia, and agraphia. As the disease progresses, muscle weakness begins to affect the other limbs and respiratory muscles, ultimately resulting in respiratory or cardiac failure.
Disease Hierarchy	DIS6SVEE: Syndromic disease DISDUT8O: Hereditary inclusion-body myopathy DISKYHXL: Frontotemporal dementia DISK4S94: Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
Disease Identifiers	MONDO ID MONDO_0000507 MESH ID C563476 UMLS CUI C1833662 MedGen ID 322251 Orphanet ID 52430 SNOMED CT ID 703544004

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
VCP	OTWIX1JU	Definitive	Autosomal dominant	[1]
ACTA1	OTOVGLPG	Disputed	Altered Expression	[6]
HNRNPA1	OTIRPN6B	Supportive	Autosomal dominant	[3]
HNRNPA2B1	OTBZKX4P	Supportive	Autosomal dominant	[3]
AAAS	OTJT9T23	Strong	Genetic Variation	[7]
CFDP1	OTXY7J96	Strong	Genetic Variation	[8]
EIF4G2	OTEO98CR	Strong	Genetic Variation	[8]
GEMIN4	OTX7402E	Strong	Genetic Variation	[8]
MASP1	OTWWCNZP	Strong	Biomarker	[9]
MOAP1	OTVF3LUG	Strong	Biomarker	[9]
NMS	OTFYS4LO	Strong	Genetic Variation	[10]
PSMD2	OT6HZHN7	Strong	Genetic Variation	[8]
SHOC2	OTUNQ2CT	Strong	Biomarker	[11]
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⏷ Show the Full List of 13 DOT(s)

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
VCP	TTHNLSB	Limited	Genetic Variation	[2]
HNRNPA1	TTPJ9XK	Supportive	Autosomal dominant	[3]
HNRNPA2B1	TT8UPW6	Supportive	Autosomal dominant	[3]
GNE	TT4DP5S	Strong	Genetic Variation	[4]
HNRNPA1	TTPJ9XK	Strong	GermlineCausalMutation	[3]
HNRNPA2B1	TT8UPW6	Strong	GermlineCausalMutation	[3]
TARDBP	TT9RZ03	Strong	Genetic Variation	[5]
VCP	TTYWTI0	Definitive	Autosomal dominant	[1]
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⏷ Show the Full List of 8 DTT(s)

References

1	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.
2	Distal myopathy and rapidly progressive dementia associated with a novel mutation in the VCP gene: Expanding inclusion body myopathy with early-onset Paget disease and frontotemporal dementia spectrum.J Clin Neurosci. 2019 Jun;64:8-10. doi: 10.1016/j.jocn.2019.03.063. Epub 2019 Apr 4.
3	Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3.
4	Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes.Neuromuscul Disord. 2003 Sep;13(7-8):559-67. doi: 10.1016/s0960-8966(03)00070-1.
5	Neuronal-specific overexpression of a mutant valosin-containing protein associated with IBMPFD promotes aberrant ubiquitin and TDP-43 accumulation and cognitive dysfunction in transgenic mice.Am J Pathol. 2013 Aug;183(2):504-15. doi: 10.1016/j.ajpath.2013.04.014. Epub 2013 Jun 5.
6	VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle.Autophagy. 2019 Jun;15(6):1082-1099. doi: 10.1080/15548627.2019.1569933. Epub 2019 Jan 29.
7	A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.Sci Rep. 2017 Mar 17;7:44751. doi: 10.1038/srep44751.
8	ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.Mol Cell. 2018 Jun 7;70(5):906-919.e7. doi: 10.1016/j.molcel.2018.04.021. Epub 2018 May 24.
9	Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease.J Cell Biol. 2009 Dec 14;187(6):875-88. doi: 10.1083/jcb.200908115.
10	Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.J Mol Biol. 2014 Jul 29;426(15):2886-99. doi: 10.1016/j.jmb.2014.05.022. Epub 2014 May 27.
11	VCP/p97 controls signals of the ERK1/2 pathway transmitted via the Shoc2 scaffolding complex: novel insights into IBMPFD pathology.Mol Biol Cell. 2019 Jul 1;30(14):1655-1663. doi: 10.1091/mbc.E19-03-0144. Epub 2019 May 15.