NEM7
MCID: NML010
MIFTS: 40

Nemaline Myopathy 7 (NEM7)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Nemaline Myopathy 7

MalaCards integrated aliases for Nemaline Myopathy 7:

Name: Nemaline Myopathy 7 56 12 73 29 13 6 15 71
Nemaline Myopathy 7, Autosomal Recessive 56 12 73 29
Nem7 56 12 73
Cfl2-Related Nemaline Myopathy 73
Myopathy, Nemaline, Type 7 39

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
onset in early childhood
two unrelated families have been reported (last curated august 2013)


HPO:

31
nemaline myopathy 7:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:



External Ids:

Disease Ontology 12 DOID:0110934
OMIM 56 610687
OMIM Phenotypic Series 56 PS161800
MeSH 43 D017696
MedGen 41 C1853154
UMLS 71 C1853154

Summaries for Nemaline Myopathy 7

OMIM : 56 Nemaline myopathy-7 is an autosomal recessive congenital myopathy characterized by very early onset of hypotonia and delayed motor development. Affected individuals have difficulty walking and running due to proximal muscle weakness. The disorder is slowly progressive, and patients may lose independent ambulation. Muscle biopsy shows nemaline rods and may later show minicores, abnormal protein aggregates, and dystrophic changes (summary by Ockeloen et al., 2012). For a discussion of genetic heterogeneity of nemaline myopathy, see 161800. (610687)

MalaCards based summary : Nemaline Myopathy 7, also known as nemaline myopathy 7, autosomal recessive, is related to nemaline myopathy 10 and nemaline myopathy 2. An important gene associated with Nemaline Myopathy 7 is CFL2 (Cofilin 2), and among its related pathways/superpathways are Sertoli-Sertoli Cell Junction Dynamics and cGMP-PKG signaling pathway. Affiliated tissues include skeletal muscle, and related phenotypes are respiratory insufficiency due to muscle weakness and muscular hypotonia

Disease Ontology : 12 A nemaline myopathy characterized by very early onset of hypotonia and delayed motor development that has material basis in homozygous mutation in the CFL2 gene on chromosome 14q13.

UniProtKB/Swiss-Prot : 73 Nemaline myopathy 7: A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 7 presents at birth with hypotonia and generalized weakness. Major motor milestones are delayed, but independent ambulation is achieved.

Related Diseases for Nemaline Myopathy 7

Symptoms & Phenotypes for Nemaline Myopathy 7

Human phenotypes related to Nemaline Myopathy 7:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 respiratory insufficiency due to muscle weakness 31 occasional (7.5%) HP:0002747
2 muscular hypotonia 31 HP:0001252
3 muscle weakness 31 HP:0001324
4 gait disturbance 31 HP:0001288
5 high palate 31 HP:0000218
6 nemaline bodies 31 HP:0003798
7 joint hypermobility 31 HP:0001382
8 areflexia 31 HP:0001284
9 delayed gross motor development 31 HP:0002194
10 myofibrillar myopathy 31 HP:0003715
11 generalized hypotonia 31 HP:0001290
12 minicore myopathy 31 HP:0003789
13 neck muscle weakness 31 HP:0000467
14 gowers sign 31 HP:0003391

Symptoms via clinical synopsis from OMIM:

56
Skeletal:
joint hypermobility

Head And Neck Neck:
neck muscle weakness

Neurologic Central Nervous System:
abnormal gait
delayed motor development
loss of independent ambulation (in some patients)

Respiratory:
respiratory insufficiency due to muscle weakness (in some patients)

Neurologic Peripheral Nervous System:
areflexia

Muscle Soft Tissue:
gowers sign
hypotonia
type 1 fiber predominance
muscle weakness, mainly proximal and axial
fiber type variation seen on biopsy
more
Head And Neck Mouth:
high-arched palate

Clinical features from OMIM:

610687

GenomeRNAi Phenotypes related to Nemaline Myopathy 7 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Upregulation of Wnt/beta-catenin pathway after WNT3A stimulation GR00016-A 8.92 GUCY1A2 NPR1 POLR2C POLR2D

Drugs & Therapeutics for Nemaline Myopathy 7

Search Clinical Trials , NIH Clinical Center for Nemaline Myopathy 7

Genetic Tests for Nemaline Myopathy 7

Genetic tests related to Nemaline Myopathy 7:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 7 29 CFL2
2 Nemaline Myopathy 7, Autosomal Recessive 29

Anatomical Context for Nemaline Myopathy 7

MalaCards organs/tissues related to Nemaline Myopathy 7:

40
Skeletal Muscle

Publications for Nemaline Myopathy 7

Articles related to Nemaline Myopathy 7:

# Title Authors PMID Year
1
Congenital myopathy caused by a novel missense mutation in the CFL2 gene. 56 6
22560515 2012
2
Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. 56 6
17160903 2007
3
Clinical utility gene card for: nemaline myopathy. 6
22510848 2012
4
Nemaline Myopathy – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 6
20301465 2002
5
Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. 61
23394784 2013

Variations for Nemaline Myopathy 7

ClinVar genetic disease variations for Nemaline Myopathy 7:

6 (show top 50) (show all 56) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CFL2 NC_000014.9:g.(?_34712845)_(34714560_?)deldeletion Pathogenic 583485 14:35182051-35183766 14:34712845-34714560
2 CFL2 NC_000014.9:g.(?_34710372)_(34713686_?)deldeletion Pathogenic 657372 14:35179578-35182892 14:34710372-34713686
3 CFL2 NM_138638.5(CFL2):c.338del (p.Ser113fs)deletion Pathogenic 800930 14:35182316-35182316 14:34713110-34713110
4 CFL2 NM_138638.5(CFL2):c.103G>A (p.Ala35Thr)SNV Pathogenic 8160 rs80358250 14:35182668-35182668 14:34713462-34713462
5 CFL2 NM_138638.5(CFL2):c.21G>A (p.Val7=)SNV Conflicting interpretations of pathogenicity 195369 rs149700171 14:35182750-35182750 14:34713544-34713544
6 CFL2 NM_138638.5(CFL2):c.4-198A>GSNV Uncertain significance 313098 rs143465827 14:35182965-35182965 14:34713759-34713759
7 CFL2 NM_138638.5(CFL2):c.76C>G (p.Gln26Glu)SNV Uncertain significance 882972 14:35182695-35182695 14:34713489-34713489
8 CFL2 NM_138638.5(CFL2):c.19G>A (p.Val7Met)SNV Uncertain significance 60554 rs397515451 14:35182752-35182752 14:34713546-34713546
9 CFL2 NM_138638.5(CFL2):c.457T>G (p.Leu153Val)SNV Uncertain significance 128713 rs587780312 14:35182115-35182115 14:34712909-34712909
10 CFL2 NM_138638.5(CFL2):c.*473A>GSNV Uncertain significance 881820 14:35181598-35181598 14:34712392-34712392
11 CFL2 NM_138638.5(CFL2):c.*281A>GSNV Uncertain significance 882970 14:35181790-35181790 14:34712584-34712584
12 CFL2 NM_138638.5(CFL2):c.*995T>CSNV Uncertain significance 313087 rs749572493 14:35181076-35181076 14:34711870-34711870
13 CFL2 NM_138638.5(CFL2):c.*541A>GSNV Uncertain significance 313090 rs144345993 14:35181530-35181530 14:34712324-34712324
14 CFL2 NM_138638.5(CFL2):c.*362G>ASNV Uncertain significance 313092 rs553554454 14:35181709-35181709 14:34712503-34712503
15 CFL2 NM_138638.5(CFL2):c.*718A>GSNV Uncertain significance 313089 rs886050474 14:35181353-35181353 14:34712147-34712147
16 CFL2 NM_138638.5(CFL2):c.*2340T>GSNV Uncertain significance 313075 rs886050473 14:35179731-35179731 14:34710525-34710525
17 CFL2 NC_000014.9:g.(?_34710372)_(34713686_?)dupduplication Uncertain significance 833241 14:35179578-35182892
18 CFL2 NM_138638.5(CFL2):c.17C>G (p.Thr6Arg)SNV Uncertain significance 840465 14:35182754-35182754 14:34713548-34713548
19 CFL2 NM_138638.5(CFL2):c.*2248G>ASNV Uncertain significance 882916 14:35179823-35179823 14:34710617-34710617
20 CFL2 NM_138638.5(CFL2):c.*1886G>ASNV Uncertain significance 882917 14:35180185-35180185 14:34710979-34710979
21 CFL2 NM_138638.5(CFL2):c.*1810T>ASNV Uncertain significance 883712 14:35180261-35180261 14:34711055-34711055
22 CFL2 NM_138638.5(CFL2):c.*1759A>GSNV Uncertain significance 883713 14:35180312-35180312 14:34711106-34711106
23 CFL2 NM_138638.5(CFL2):c.*1620T>CSNV Uncertain significance 883714 14:35180451-35180451 14:34711245-34711245
24 CFL2 NM_138638.5(CFL2):c.*1507C>TSNV Uncertain significance 883715 14:35180564-35180564 14:34711358-34711358
25 CFL2 NM_138638.5(CFL2):c.388G>C (p.Gly130Arg)SNV Uncertain significance 583009 rs1566525113 14:35182266-35182266 14:34713060-34713060
26 CFL2 NC_000014.8:g.(?_35182051)_(35183766_?)dupduplication Uncertain significance 583711 14:35182051-35183766 14:34712845-34714560
27 CFL2 NM_138638.5(CFL2):c.471_473AGT[1] (p.Val159del)short repeat Uncertain significance 662117 14:35182096-35182098 14:34712890-34712892
28 CFL2 NM_138638.5(CFL2):c.328C>T (p.Pro110Ser)SNV Uncertain significance 650607 14:35182326-35182326 14:34713120-34713120
29 CFL2 NM_138638.5(CFL2):c.54G>A (p.Met18Ile)SNV Uncertain significance 661578 14:35182717-35182717 14:34713511-34713511
30 CFL2 NM_138638.5(CFL2):c.*1030C>GSNV Uncertain significance 881372 14:35181041-35181041 14:34711835-34711835
31 CFL2 NM_138638.5(CFL2):c.*738A>GSNV Uncertain significance 881374 14:35181333-35181333 14:34712127-34712127
32 CFL2 NM_138638.5(CFL2):c.*720A>TSNV Uncertain significance 881375 14:35181351-35181351 14:34712145-34712145
33 CFL2 NM_138638.5(CFL2):c.*293G>ASNV Uncertain significance 313093 rs774843860 14:35181778-35181778 14:34712572-34712572
34 CFL2 NM_138638.5(CFL2):c.4-172C>TSNV Uncertain significance 313097 rs190226324 14:35182939-35182939 14:34713733-34713733
35 CFL2 NM_138638.5(CFL2):c.*1070G>ASNV Uncertain significance 313085 rs767101584 14:35181001-35181001 14:34711795-34711795
36 CFL2 NM_138638.5(CFL2):c.*2284C>TSNV Uncertain significance 313076 rs372609152 14:35179787-35179787 14:34710581-34710581
37 CFL2 NM_138638.5(CFL2):c.*1885C>TSNV Uncertain significance 313081 rs775859581 14:35180186-35180186 14:34710980-34710980
38 CFL2 NM_138638.5(CFL2):c.*1036G>ASNV Uncertain significance 313086 rs150492527 14:35181035-35181035 14:34711829-34711829
39 CFL2 NM_138638.5(CFL2):c.*671C>TSNV Likely benign 881818 14:35181400-35181400 14:34712194-34712194
40 CFL2 NM_138638.5(CFL2):c.*605T>CSNV Likely benign 881819 14:35181466-35181466 14:34712260-34712260
41 CFL2 NM_138638.5(CFL2):c.*905A>GSNV Likely benign 881373 14:35181166-35181166 14:34711960-34711960
42 CFL2 NM_138638.5(CFL2):c.389-9deldeletion Likely benign 465805 rs1555333750 14:35182192-35182192 14:34712986-34712986
43 CFL2 NM_138638.5(CFL2):c.276A>G (p.Lys92=)SNV Likely benign 753309 14:35182495-35182495 14:34713289-34713289
44 CFL2 NM_138638.5(CFL2):c.495A>G (p.Pro165=)SNV Likely benign 743607 14:35182077-35182077 14:34712871-34712871
45 CFL2 NM_138638.5(CFL2):c.*1268C>TSNV Likely benign 883716 14:35180803-35180803 14:34711597-34711597
46 CFL2 NM_138638.5(CFL2):c.*40A>GSNV Likely benign 882971 14:35182031-35182031 14:34712825-34712825
47 CFL2 NM_138638.5(CFL2):c.255C>T (p.Tyr85=)SNV Likely benign 390982 rs1057523939 14:35182516-35182516 14:34713310-34713310
48 CFL2 NM_138638.5(CFL2):c.15T>C (p.Val5=)SNV Benign/Likely benign 261430 rs542840152 14:35182756-35182756 14:34713550-34713550
49 CFL2 NM_138638.5(CFL2):c.*1682A>TSNV Benign 313082 rs712301 14:35180389-35180389 14:34711183-34711183
50 CFL2 NM_138638.5(CFL2):c.*925T>CSNV Benign 313088 rs11539496 14:35181146-35181146 14:34711940-34711940

UniProtKB/Swiss-Prot genetic disease variations for Nemaline Myopathy 7:

73
# Symbol AA change Variation ID SNP ID
1 CFL2 p.Ala35Thr VAR_031989 rs80358250

Expression for Nemaline Myopathy 7

Search GEO for disease gene expression data for Nemaline Myopathy 7.

Pathways for Nemaline Myopathy 7

Pathways related to Nemaline Myopathy 7 according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.46 NPR1 GUCY1B1 GUCY1A2 CFL2
2
Show member pathways
12.19 NPR1 GUCY1B1 GUCY1A2
3
Show member pathways
12.11 NPR1 GUCY1B1 GUCY1A2
4
Show member pathways
11.7 NPR1 GUCY1B1 GUCY1A2 CTPS2 CTPS1
5 11.48 POLR2D POLR2C
6 11.31 GUCY1B1 GUCY1A2
7 11.3 NPR1 GUCY1B1 GUCY1A2
8 11.25 POLR2D POLR2C
9
Show member pathways
11.18 POLR2D POLR2C
10
Show member pathways
11.08 GUCY1B1 GUCY1A2
11 10.97 NPR1 GUCY1B1 GUCY1A2
12 10.9 POLR2D POLR2C
13 10.85 GUCY1B1 GUCY1A2
14 10.72 CTPS2 CTPS1
15 10.37 GUCY1B1 GUCY1A2

GO Terms for Nemaline Myopathy 7

Cellular components related to Nemaline Myopathy 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II, core complex GO:0005665 8.96 POLR2D POLR2C
2 cytoophidium GO:0097268 8.62 CTPS2 CTPS1

Biological processes related to Nemaline Myopathy 7 according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 regulation of gene silencing by miRNA GO:0060964 9.58 POLR2D POLR2C
2 fibroblast growth factor receptor signaling pathway GO:0008543 9.57 POLR2D POLR2C
3 transcription elongation from RNA polymerase II promoter GO:0006368 9.56 POLR2D POLR2C
4 transcription-coupled nucleotide-excision repair GO:0006283 9.55 POLR2D POLR2C
5 snRNA transcription by RNA polymerase II GO:0042795 9.54 POLR2D POLR2C
6 somatic stem cell population maintenance GO:0035019 9.52 POLR2D POLR2C
7 RNA metabolic process GO:0016070 9.51 POLR2D POLR2C
8 7-methylguanosine mRNA capping GO:0006370 9.49 POLR2D POLR2C
9 positive regulation of viral transcription GO:0050434 9.48 POLR2D POLR2C
10 nucleobase-containing small molecule interconversion GO:0015949 9.46 CTPS2 CTPS1
11 cGMP-mediated signaling GO:0019934 9.43 NPR1 GUCY1B1
12 glutamine metabolic process GO:0006541 9.4 CTPS2 CTPS1
13 CTP biosynthetic process GO:0006241 9.37 CTPS2 CTPS1
14 pyrimidine nucleotide biosynthetic process GO:0006221 9.32 CTPS2 CTPS1
15 pyrimidine nucleobase biosynthetic process GO:0019856 9.26 CTPS2 CTPS1
16 'de novo' CTP biosynthetic process GO:0044210 9.16 CTPS2 CTPS1
17 cyclic nucleotide biosynthetic process GO:0009190 9.13 NPR1 GUCY1B1 GUCY1A2
18 cGMP biosynthetic process GO:0006182 8.8 NPR1 GUCY1B1 GUCY1A2

Molecular functions related to Nemaline Myopathy 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.73 POLR2D NPR1 GUCY1B1 GUCY1A2 CTPS2 CTPS1
2 GTP binding GO:0005525 9.58 NPR1 GUCY1B1 GUCY1A2
3 lyase activity GO:0016829 9.5 NPR1 GUCY1B1 GUCY1A2
4 DNA-directed 5'-3' RNA polymerase activity GO:0003899 9.37 POLR2D POLR2C
5 CTP synthase activity GO:0003883 9.16 CTPS2 CTPS1
6 phosphorus-oxygen lyase activity GO:0016849 9.13 NPR1 GUCY1B1 GUCY1A2
7 guanylate cyclase activity GO:0004383 8.8 NPR1 GUCY1B1 GUCY1A2

Sources for Nemaline Myopathy 7

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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