Details of Disease

Disease Name

Kennedy disease

spinal and bulbar muscular atrophy; spinal and bulbar muscular atrophy, X-linked 1; bulbospinal neuronopathy, X-linked recessive; Kennedy spinal and bulbar muscular atrophy; bulbospinal muscular atrophy, X-linked; SBMA; X-linked BSMA; X-linked bulbospinal muscular atrophy; X-linked spinal and bulbar muscular atrophy; Kennedy's disease; spinal and bulbar muscular atrophy of Kennedy, X-linked recessive; spinal and bulbar muscular atrophy, X-linked type 1; X-linked bulbo-spinal atrophy; Kennedy disease; SMAX1; spinal bulbar muscular atrophy; X-linked bulbospinal amyotrophy; spinobulbar muscular atrophy

Definition

Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare X-linked recessive motor neuron disease characterized by proximal and bulbar muscle wasting.

Disease Hierarchy

DISPN7D2: Inherited neurodegenerative disorder

DISXZVM1: Kennedy disease

Disease Identifiers

MONDO ID

MONDO_0010735

MESH ID

D055534

UMLS CUI

C1839259

OMIM ID

313200

MedGen ID

333282

Orphanet ID

481

General Information of Disease (ID: DISXZVM1)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DMPK	TTZQTY2	Limited	Genetic Variation	[1]
GRIA2	TTWM461	Limited	Altered Expression	[2]
GRM2	TTXJ47W	Limited	Altered Expression	[2]
SCN3A	TTAXZ0K	Limited	Altered Expression	[3]
NLRX1	TTKT026	Disputed	Altered Expression	[4]
ATXN3	TT6A17J	Strong	Biomarker	[5]
DNAJB1	TTPXAWS	Strong	Biomarker	[6]
HSPB8	TTY0OJN	Strong	Biomarker	[7]
HTT	TTIWZ0O	Strong	Biomarker	[8]
TRIP10	TTKHTGE	Strong	Genetic Variation	[9]
AR	TTS64P2	Definitive	X-linked	[10]
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⏷ Show the Full List of 11 DTT(s)

This Disease Is Related to 30 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BPTF	OTD1RZAD	Limited	Biomarker	[11]
CELF2	OTLJJ4VT	Limited	Posttranslational Modification	[12]
COX5B	OTDP94F3	Limited	Biomarker	[13]
FAM135B	OTCSYBI7	Limited	Biomarker	[14]
HES5	OTW7JEHV	Limited	Altered Expression	[15]
HSPH1	OTVRR73T	Limited	Altered Expression	[16]
LY6E	OTMG16BZ	Limited	Genetic Variation	[17]
MAP7	OTVSSJ33	Limited	Biomarker	[18]
MYO5B	OTCKL3W3	Limited	Genetic Variation	[19]
NRF1	OTOXWNV8	Limited	Biomarker	[20]
OTX2	OTTV05B1	Limited	Biomarker	[21]
PRMT6	OT5V3XIN	Limited	Genetic Variation	[22]
PSME3	OTSTC4YY	Limited	Altered Expression	[23]
SEMA3B	OTCZCPMS	Limited	Genetic Variation	[21]
SEPTIN7	OTJI08YX	Limited	Biomarker	[18]
STOML1	OTSIO2QA	Limited	Altered Expression	[24]
SUCO	OT3I9VO9	Limited	Altered Expression	[24]
SYTL1	OTP0R3S5	Limited	Altered Expression	[24]
ATXN1	OTQF0HNR	moderate	Biomarker	[25]
CERS6	OTOP4GV1	moderate	Biomarker	[26]
IGFALS	OTTWCZYM	moderate	Biomarker	[27]
CHCHD10	OTCDHAM6	Strong	Biomarker	[28]
DNAJA1	OT38BZQQ	Strong	Biomarker	[6]
DNAJB2	OTZHPV5M	Strong	Altered Expression	[29]
GFRA1	OT3WBVYB	Strong	Altered Expression	[30]
HAP1	OT6SG0JQ	Strong	Biomarker	[8]
KAT2A	OTN0W2SW	Strong	Biomarker	[31]
MYH8	OT9F350W	Strong	Biomarker	[28]
NEFH	OTMSCW5I	Strong	Altered Expression	[32]
AR	OTUBKAZZ	Definitive	X-linked	[10]
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⏷ Show the Full List of 30 DOT(s)

References

1	Association of spinal and bulbar muscular atrophy with myotonic dystrophy type 1.Muscle Nerve. 2004 May;29(5):729-33. doi: 10.1002/mus.10556.
2	Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA.Neurosci Res. 2006 Jan;54(1):11-4. doi: 10.1016/j.neures.2005.09.006. Epub 2005 Oct 12.
3	GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions.Neuropharmacology. 2017 Feb;113(Pt A):480-489. doi: 10.1016/j.neuropharm.2016.11.002. Epub 2016 Nov 2.
4	NOD-like receptor X1 functions as a tumor suppressor by inhibiting epithelial-mesenchymal transition and inducing aging in hepatocellular carcinoma cells.J Hematol Oncol. 2018 Feb 26;11(1):28. doi: 10.1186/s13045-018-0573-9.
5	Polyglutamine (PolyQ) diseases: genetics to treatments.Cell Transplant. 2014;23(4-5):441-58. doi: 10.3727/096368914X678454.
6	Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease.Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2898-903. doi: 10.1073/pnas.97.6.2898.
7	The Role of the Heat Shock Protein B8 (HSPB8) in Motoneuron Diseases.Front Mol Neurosci. 2017 Jun 21;10:176. doi: 10.3389/fnmol.2017.00176. eCollection 2017.
8	Immunohistochemical analysis of huntingtin-associated protein 1 in adult rat spinal cord and its regional relationship with androgen receptor.Neuroscience. 2017 Jan 6;340:201-217. doi: 10.1016/j.neuroscience.2016.10.053. Epub 2016 Oct 29.
9	CIP4 promotes lung adenocarcinoma metastasis and is associated with poor prognosis.Oncogene. 2015 Jul;34(27):3527-35. doi: 10.1038/onc.2014.280. Epub 2014 Sep 1.
10	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.
11	BPTF inhibits NK cell activity and the abundance of natural cytotoxicity receptor co-ligands.Oncotarget. 2017 May 12;8(38):64344-64357. doi: 10.18632/oncotarget.17834. eCollection 2017 Sep 8.
12	Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of CELF2.Nat Med. 2012 Jul;18(7):1136-41. doi: 10.1038/nm.2791.
13	Cytochrome c oxidase subunit Vb interacts with human androgen receptor: a potential mechanism for neurotoxicity in spinobulbar muscular atrophy.Brain Res Bull. 2001 Oct-Nov 1;56(3-4):285-97. doi: 10.1016/s0361-9230(01)00583-4.
14	Phenotypic and molecular features underlying neurodegeneration of motor neurons derived from spinal and bulbar muscular atrophy patients.Neurobiol Dis. 2019 Apr;124:1-13. doi: 10.1016/j.nbd.2018.10.019. Epub 2018 Nov 1.
15	DNA methylation inhibitor attenuates polyglutamine-induced neurodegeneration by regulating Hes5.EMBO Mol Med. 2019 May;11(5):e8547. doi: 10.15252/emmm.201708547.
16	Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease.Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16801-6. doi: 10.1073/pnas.0506249102. Epub 2005 Oct 31.
17	Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation.Nat Genet. 1997 Feb;15(2):197-200. doi: 10.1038/ng0297-197.
18	Septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing.J Cell Sci. 2018 Jun 28;131(12):jcs212647. doi: 10.1242/jcs.212647.
19	Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease.J Clin Invest. 2014 Jul;124(7):2947-62. doi: 10.1172/JCI71651. Epub 2014 Jun 2.
20	A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy.Hum Mol Genet. 2016 May 15;25(10):1979-1989. doi: 10.1093/hmg/ddw073. Epub 2016 Mar 8.
21	Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.Mol Oncol. 2018 Apr;12(4):495-513. doi: 10.1002/1878-0261.12177. Epub 2018 Mar 1.
22	Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy.Neuron. 2015 Jan 7;85(1):88-100. doi: 10.1016/j.neuron.2014.12.031.
23	The 11S Proteasomal Activator REG Impacts Polyglutamine-Expanded Androgen Receptor Aggregation and Motor Neuron Viability through Distinct Mechanisms.Front Mol Neurosci. 2017 May 24;10:159. doi: 10.3389/fnmol.2017.00159. eCollection 2017.
24	CD24 cell surface expression in Mvt1 mammary cancer cells serves as a biomarker for sensitivity to anti-IGF1R therapy.Breast Cancer Res. 2016 May 14;18(1):51. doi: 10.1186/s13058-016-0711-7.
25	The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology.Handb Clin Neurol. 2018;147:143-170. doi: 10.1016/B978-0-444-63233-3.00011-7.
26	The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach.Mol Metab. 2019 Mar;21:36-50. doi: 10.1016/j.molmet.2018.12.008. Epub 2019 Jan 2.
27	Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy.Neurology. 2019 Mar 12;92(11):e1205-e1211. doi: 10.1212/WNL.0000000000007097. Epub 2019 Feb 20.
28	Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.PLoS One. 2016 Mar 21;11(3):e0151376. doi: 10.1371/journal.pone.0151376. eCollection 2016.
29	DNAJB2 expression in normal and diseased human and mouse skeletal muscle.Am J Pathol. 2010 Jun;176(6):2901-10. doi: 10.2353/ajpath.2010.090663. Epub 2010 Apr 15.
30	Expression of GDNF and GDNFR-alpha mRNAs in muscles of patients with motor neuron diseases.Neurochem Res. 1999 Jun;24(6):785-90. doi: 10.1023/a:1020739831778.
31	GCN-5/PGC-1 signaling is activated and associated with metabolism in cyclin E1-driven ovarian cancer.Aging (Albany NY). 2019 Jul 17;11(14):4890-4899. doi: 10.18632/aging.102082.
32	Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy.J Neurosci. 2004 May 19;24(20):4778-86. doi: 10.1523/JNEUROSCI.0808-04.2004.