Details of Disease

Disease Name

Nemaline myopathy

Rod-body myopathy; Rod body disease; congenital rod disease; nemaline rod disease; nemaline rod myopathy; nemaline myopathy; rod myopathy; NM; NEM; nemaline body disease

Definition

Nemaline myopathy (NM) encompasses a large spectrum of myopathies characterized by hypotonia, weakness and depressed or absent deep tendon reflexes, with pathologic evidence of nemaline bodies (rods) on muscle biopsy.

Disease Hierarchy

DISZ9JP4: Congenital structural myopathy

DIS5IYLY: Nemaline myopathy

Disease Identifiers

MONDO ID

MONDO_0018958

MESH ID

D017696

UMLS CUI

C0206157

MedGen ID

61528

Orphanet ID

607

SNOMED CT ID

75072002

General Information of Disease (ID: DIS5IYLY)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CUL3	TTPCU0Q	Strong	Biomarker	[1]
MSTN	TTM8I2X	Strong	Biomarker	[2]
RYR1	TTU5CIX	Strong	Genetic Variation	[3]
GJB6	TTAU8SJ	Definitive	Genetic Variation	[4]
MCOLN1	TT9XBVO	Definitive	Genetic Variation	[4]
UCP3	TT12RJK	Definitive	Altered Expression	[5]
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⏷ Show the Full List of 6 DTT(s)

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHKB	DEHWR6V	Strong	Biomarker	[6]
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This Disease Is Related to 26 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KLHL41	OTLABE56	Limited	Biomarker	[7]
LMNA	OT3SG7ZR	Limited	Biomarker	[8]
MYOT	OTCEW5XW	Limited	Biomarker	[9]
RIF1	OTPE49OE	Limited	Genetic Variation	[10]
TNNT1	OT8PBOAR	Limited	Autosomal dominant	[11]
KBTBD13	OTN5QRKV	Disputed	Genetic Variation	[12]
NEFL	OTQESJV4	moderate	Biomarker	[13]
TNNT3	OT4C498E	Moderate	Autosomal recessive	[14]
ACTC1	OTJU04B1	Strong	Genetic Variation	[15]
B4GAT1	OT5NH9TD	Strong	Biomarker	[16]
CFL2	OTE2W0DH	Strong	Biomarker	[17]
FKRP	OTMUZ7GH	Strong	Biomarker	[18]
FKTN	OTQ9GCXL	Strong	Biomarker	[19]
ITGA7	OTTBTAYW	Strong	Biomarker	[20]
LARGE1	OTUH7H9F	Strong	Biomarker	[21]
LMOD3	OTSJ3QGX	Strong	Biomarker	[22]
MYPN	OTHTOFDU	Strong	Genetic Variation	[23]
NEB	OT7P9IR3	Strong	Biomarker	[24]
POMGNT1	OTBNOUZC	Strong	Biomarker	[18]
ACTN1	OTUCLNXH	Definitive	Biomarker	[1]
C16orf82	OT77Z5Y5	Definitive	Genetic Variation	[25]
EIF3K	OTGTKVGO	Definitive	Biomarker	[26]
KLHL9	OTRGEG3Z	Definitive	Biomarker	[27]
MYO18B	OTGYY4NK	Definitive	Genetic Variation	[28]
NRAP	OTO6H3YF	Definitive	Biomarker	[7]
SRPK3	OT239QMC	Definitive	Biomarker	[29]
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⏷ Show the Full List of 26 DOT(s)

References

1	Cullin-3 dependent deregulation of ACTN1 represents a new pathogenic mechanism in nemaline myopathy.JCI Insight. 2019 Apr 16;5(10):e125665. doi: 10.1172/jci.insight.125665.
2	Myostatin Inhibition Using ActRIIB-mFc Does Not Produce Weight Gain or Strength in the Nebulin Conditional KO Mouse.J Neuropathol Exp Neurol. 2019 Feb 1;78(2):130-139. doi: 10.1093/jnen/nly120.
3	Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing.Am J Med Genet A. 2012 Apr;158A(4):772-8. doi: 10.1002/ajmg.a.35243. Epub 2012 Mar 9.
4	Development of TaqMan allelic discrimination based genotyping of large DNA deletions.Genomics. 2012 Mar;99(3):127-31. doi: 10.1016/j.ygeno.2012.01.003. Epub 2012 Jan 17.
5	Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle.Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4666-71. doi: 10.1073/pnas.0330960100. Epub 2003 Apr 3.
6	A rostrocaudal muscular dystrophy caused by a defect in choline kinase beta, the first enzyme in phosphatidylcholine biosynthesis.J Biol Chem. 2006 Feb 24;281(8):4938-48. doi: 10.1074/jbc.M512578200. Epub 2005 Dec 21.
7	Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy.Hum Mol Genet. 2019 Aug 1;28(15):2549-2560. doi: 10.1093/hmg/ddz078.
8	DelK32-lamin A/C has abnormal location and induces incomplete tissue maturation and severe metabolic defects leading to premature death.Hum Mol Genet. 2012 Mar 1;21(5):1037-48. doi: 10.1093/hmg/ddr534. Epub 2011 Nov 16.
9	Beyond LGMD1A: myotilin is a component of central core lesions and nemaline rods.Neuromuscul Disord. 2003 Aug;13(6):451-5. doi: 10.1016/s0960-8966(03)00064-6.
10	Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing.Orphanet J Rare Dis. 2016 Jan 25;11:8. doi: 10.1186/s13023-016-0390-6.
11	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.
12	A family with nemaline myopathy type 6 caused by hseterozygous mutation (c.1222C>T) in the KBTBD13 gene in China: A case report.Neuropathology. 2020 Feb;40(1):104-108. doi: 10.1111/neup.12610. Epub 2019 Dec 11.
13	Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.JAMA Neurol. 2014 Nov;71(11):1413-20. doi: 10.1001/jamaneurol.2014.1432.
14	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
15	Functional effects of nemaline myopathy mutations on human skeletal alpha-actin.J Biol Chem. 2008 Jul 11;283(28):19379-88. doi: 10.1074/jbc.M801963200. Epub 2008 May 12.
16	Dystroglycan organizes axon guidance cue localization and axonal pathfinding.Neuron. 2012 Dec 6;76(5):931-44. doi: 10.1016/j.neuron.2012.10.009.
17	Cofilin-2 phosphorylation and sequestration in myocardial aggregates: novel pathogenetic mechanisms for idiopathic dilated cardiomyopathy.J Am Coll Cardiol. 2015 Mar 31;65(12):1199-1214. doi: 10.1016/j.jacc.2015.01.031.
18	Degree of Cajal-Retzius Cell Mislocalization Correlates with the Severity of Structural Brain Defects in Mouse Models of Dystroglycanopathy.Brain Pathol. 2016 Jul;26(4):465-78. doi: 10.1111/bpa.12306. Epub 2015 Oct 12.
19	Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.Hum Mol Genet. 2009 Feb 15;18(4):621-31. doi: 10.1093/hmg/ddn387. Epub 2008 Nov 18.
20	61 and 71 integrins are required in Schwann cells to sort axons.J Neurosci. 2013 Nov 13;33(46):17995-8007. doi: 10.1523/JNEUROSCI.3179-13.2013.
21	Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases.Mol Cell Neurosci. 2005 Oct;30(2):160-72. doi: 10.1016/j.mcn.2005.07.009.
22	Long-term follow-up and characteristic pathological findings in severe nemaline myopathy due to LMOD3 mutations. Neuromuscul Disord. 2019 Feb;29(2):108-113. doi: 10.1016/j.nmd.2018.12.009. Epub 2018 Dec 20.
23	Biallelic Mutations in MYPN, Encoding Myopalladin, Are Associated with Childhood-Onset, Slowly Progressive Nemaline Myopathy. Am J Hum Genet. 2017 Jan 5;100(1):169-178. doi: 10.1016/j.ajhg.2016.11.017. Epub 2016 Dec 22.
24	Deleting nebulin's C-terminus reveals its importance to sarcomeric structure and function and is sufficient to invoke nemaline myopathy.Hum Mol Genet. 2019 May 15;28(10):1709-1725. doi: 10.1093/hmg/ddz016.
25	Truncation by Glu180 nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy.J Biol Chem. 2003 Jul 11;278(28):26159-65. doi: 10.1074/jbc.M303469200. Epub 2003 May 5.
26	KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase.Biochem Biophys Res Commun. 2012 May 18;421(4):743-9. doi: 10.1016/j.bbrc.2012.04.074. Epub 2012 Apr 20.
27	Kelch-like homologue 9 mutation is associated with an early onset autosomal dominant distal myopathy.Brain. 2010 Jul;133(Pt 7):2123-35. doi: 10.1093/brain/awq108. Epub 2010 Jun 16.
28	A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B.Genetics. 2017 Feb;205(2):725-735. doi: 10.1534/genetics.116.192864. Epub 2016 Nov 22.
29	Next generation sequencing reveals ryanodine receptor 1 mutations in a Chinese central core disease cohort.Muscle Nerve. 2016 Sep;54(3):432-8. doi: 10.1002/mus.25050. Epub 2016 May 25.