CHN2
MCID: NRP064
MIFTS: 32

Neuropathy, Congenital Hypomyelinating, 2 (CHN2)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neuropathy, Congenital Hypomyelinating, 2

MalaCards integrated aliases for Neuropathy, Congenital Hypomyelinating, 2:

Name: Neuropathy, Congenital Hypomyelinating, 2 57 74
Hypomyelinating Neuropathy, Congenital, 2 57 74
Congenital Hypomyelinating Neuropathy 2 29 6
Chn2 57 74

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
onset at birth or in utero


HPO:

32
neuropathy, congenital hypomyelinating, 2:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:



External Ids:

MeSH 44 D015417

Summaries for Neuropathy, Congenital Hypomyelinating, 2

OMIM : 57 Congenital hypomyelinating neuropathy-2 is an autosomal dominant neurologic disorder characterized by early-onset hypotonia, severely delayed motor development, muscle weakness with areflexia, and severely decreased nerve conduction velocities (NCV) resulting from improper myelination of axons. The severity is variable: some patients may present at birth with contractures and respiratory insufficiency, whereas others may achieve walking (summary by Warner et al., 1996). CHN shows significant phenotypic overlap with Dejerine-Sottas syndrome (DSS; 145900), which is also a neuropathy with early onset. Some classify the disorders differently, noting that CHN is characterized by hypo- or amyelination resulting from a congenital defect in myelin formation, whereas DSS has features of continuous myelin breakdown, with demyelination and remyelination (summary by Smit et al., 2008). For a discussion of genetic heterogeneity of CHN, see CHN1 (605253). (618184)

MalaCards based summary : Neuropathy, Congenital Hypomyelinating, 2, also known as hypomyelinating neuropathy, congenital, 2, is related to schizophrenia and kuru. An important gene associated with Neuropathy, Congenital Hypomyelinating, 2 is MPZ (Myelin Protein Zero). Affiliated tissues include liver, skeletal muscle and brain, and related phenotypes are scoliosis and respiratory insufficiency due to muscle weakness

UniProtKB/Swiss-Prot : 74 Neuropathy, congenital hypomyelinating, 2: A form of congenital hypomyelinating neuropathy, a neurologic disorder characterized by early-onset hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (NCV) resulting from improper myelination of axons. In its extreme form, it may present with severe joint contractures or arthrogryposis multiplex congenita and respiratory insufficiency. In less severe cases patients may achieve walking. Patients lack both active myelin breakdown and well-organized onion bulbs on sural nerve biopsies, have absence of inflammation, and show hypomyelination of most or all fibers. CHN2 inheritance is autosomal dominant.

Related Diseases for Neuropathy, Congenital Hypomyelinating, 2

Diseases in the Neuropathy, Congenital Hypomyelinating, 1, Autosomal Recessive family:

Neuropathy, Congenital Hypomyelinating, 2 Neuropathy, Congenital Hypomyelinating, 3

Diseases related to Neuropathy, Congenital Hypomyelinating, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 schizophrenia 11.4
2 kuru 11.4
3 hepatosplenic t-cell lymphoma 11.4
4 diabetes mellitus, noninsulin-dependent 10.2
5 severe combined immunodeficiency 10.2
6 substance dependence 10.2

Graphical network of the top 20 diseases related to Neuropathy, Congenital Hypomyelinating, 2:



Diseases related to Neuropathy, Congenital Hypomyelinating, 2

Symptoms & Phenotypes for Neuropathy, Congenital Hypomyelinating, 2

Human phenotypes related to Neuropathy, Congenital Hypomyelinating, 2:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 scoliosis 32 HP:0002650
2 respiratory insufficiency due to muscle weakness 32 HP:0002747
3 skeletal muscle atrophy 32 HP:0003202
4 areflexia 32 HP:0001284
5 abnormality of the foot 32 HP:0001760
6 inability to walk 32 HP:0002540
7 decreased motor nerve conduction velocity 32 HP:0003431
8 decreased fetal movement 32 HP:0001558
9 hyporeflexia 32 HP:0001265
10 severe muscular hypotonia 32 HP:0006829
11 hypokinesia 32 HP:0002375
12 facial diplegia 32 HP:0001349
13 poor head control 32 HP:0002421
14 delayed ability to walk 32 HP:0031936

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
scoliosis

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
decreased motor nerve conduction velocities, severe (less than 10 m/s)
absent sensory conduction
little or no compact myelin seen on sural nerve biopsy
more
Muscle Soft Tissue:
hypokinesia
muscle atrophy
hypotonia, severe
poor fiber type differentiation caused by abnormal innervation seen on muscle biopsy

Skeletal Feet:
foot deformities

Abdomen Gastrointestinal:
poor swallowing due to muscle weakness

Skeletal Hands:
arthrogryposis of the hands

Respiratory:
respiratory insufficiency due to muscle weakness

Neurologic Central Nervous System:
inability to walk
poor head control
delayed walking
delayed motor development, severe

Head And Neck Face:
facial diplegia

Prenatal Manifestations Movement:
decreased fetal movements

Skeletal:
contractures, distal (in some patients)

Clinical features from OMIM:

618184

Drugs & Therapeutics for Neuropathy, Congenital Hypomyelinating, 2

Search Clinical Trials , NIH Clinical Center for Neuropathy, Congenital Hypomyelinating, 2

Genetic Tests for Neuropathy, Congenital Hypomyelinating, 2

Genetic tests related to Neuropathy, Congenital Hypomyelinating, 2:

# Genetic test Affiliating Genes
1 Congenital Hypomyelinating Neuropathy 2 29 MPZ

Anatomical Context for Neuropathy, Congenital Hypomyelinating, 2

MalaCards organs/tissues related to Neuropathy, Congenital Hypomyelinating, 2:

41
Liver, Skeletal Muscle, Brain, Kidney, Breast, Bone, T Cells

Publications for Neuropathy, Congenital Hypomyelinating, 2

Articles related to Neuropathy, Congenital Hypomyelinating, 2:

(show top 50) (show all 152)
# Title Authors PMID Year
1
Congenital hypomyelinating neuropathy, a long term follow-up study in an affected family. 8 71
17825553 2008
2
A novel MPZ gene mutation in congenital neuropathy with hypomyelination. 8 71
15184631 2004
3
Disturbance of muscle fiber differentiation in congenital hypomyelinating neuropathy caused by a novel myelin protein zero mutation. 8 71
12953275 2003
4
Congenital hypomyelination due to myelin protein zero Q215X mutation. 8
10319895 1999
5
Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. 8
8816708 1996
6
Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2). 38
31228090 2019
7
CHN2 Promoter Methylation Change May Be Associated With Methamphetamine Dependence. 38
29719347 2017
8
Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex. 38
26874185 2017
9
Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity. 38
28068899 2017
10
Multi-electron redox processes at a Zr(iv) center facilitated by an appended redox-active cobalt-containing metalloligand. 38
27326824 2016
11
The synthesis, structure and reactivity of an imine-stabilized carboranylphosphorus(i) compound. 38
27180610 2016
12
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. 38
27448167 2016
13
Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy. 38
26248552 2015
14
Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility. 38
26315110 2015
15
High-Resolution Array Comparative Genomic Hybridization Utility in Polish Newborns with Isolated Cleft Lip and Palate. 38
25613075 2015
16
Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients. 38
24854763 2014
17
Genome characterization of sugarcane yellow leaf virus from China reveals a novel recombinant genotype. 38
24395076 2014
18
Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study. 38
24725463 2014
19
Generation of C(2)F(5)CHN(2) in situ and its first reaction: [3+2] cycloaddition with alkenes. 38
24700600 2014
20
Influence of model grid resolution on NO2 vertical column densities over East Asia. 38
24843914 2014
21
Genome-wide association and pharmacological profiling of 29 anticancer agents using lymphoblastoid cell lines. 38
24444404 2014
22
Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease. 38
24551085 2014
23
Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. 38
25057852 2014
24
β3-chimaerin, a novel member of the chimaerin Rac-GAP family. 38
24430297 2014
25
Association of a novel polymorphism of the β2-chimaerin gene (CHN2) with smoking. 38
23941981 2013
26
Genome-wide association study of atypical psychosis. 38
24132900 2013
27
Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation. 38
23747354 2013
28
Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling. 38
23572233 2013
29
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. 38
22210626 2012
30
CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients. 38
21911749 2011
31
Genetic associations in diabetic nephropathy: a meta-analysis. 38
21127830 2011
32
Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. 38
20460425 2010
33
Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism. 38
19720790 2009
34
Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini. 38
18092178 2008
35
Comparison of cysteine peptidase activities in Trichobilharzia regenti and Schistosoma mansoni cercariae. 38
17517170 2007
36
The cysteine proteinase inhibitor Z-Phe-Ala-CHN2 alters cell morphology and cell division activity of Trypanosoma brucei bloodstream forms in vivo. 38
17328798 2007
37
The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. 38
17020538 2007
38
Labelling of four distinct trophozoite falcipains of Plasmodium falciparum by a cystatin-derived probe. 38
15899703 2005
39
Characterization of human ARHGAP10 gene in silico. 38
15375573 2004
40
Osteoclastogenesis is decreased by cysteine proteinase inhibitors. 38
15003789 2004
41
Molecular and enzymatic properties of a cathepsin L-like proteinase with distinct substrate specificity from northern shrimp (Pandalus borealis). 38
14574613 2004
42
Microarray analysis of gene-expression profiles in diffuse large B-cell lymphoma: identification of genes related to disease progression. 38
12716467 2002
43
Peptidyl diazomethyl ketones inhibit the human rhinovirus 3C protease: effect on virus yield by partial block of P3 polyprotein processing. 38
11900346 2001
44
Dipeptide vinyl sulfones suitable for intracellular inhibition of dipeptidyl peptidase I. 38
11367515 2001
45
Altered expression of cruzipain and a cathepsin B-like target in a Trypanosoma cruzi cell line displaying resistance to synthetic inhibitors of cysteine-proteinases. 38
10924756 2000
46
Trypanosoma brucei: killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2. 38
10092476 1999
47
Dipeptidyl peptidase I and III activities of adult schistosomes. 38
10205803 1999
48
Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis. 38
9869615 1999
49
Cysteine proteinase plays a key role for the initiation of yolk digestion during development of Xenopus laevis. 38
9865976 1998
50
m-Calpain subunits remain associated in the presence of calcium. 38
9801150 1998

Variations for Neuropathy, Congenital Hypomyelinating, 2

ClinVar genetic disease variations for Neuropathy, Congenital Hypomyelinating, 2:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 MPZ MPZ, 3-BP DEL/1-BP INS, NT550 indel Pathogenic
2 MPZ NM_000530.8(MPZ): c.371C> A (p.Thr124Lys) single nucleotide variant Pathogenic rs121913595 1:161276575-161276575 1:161306785-161306785
3 RHO NM_000539.3(RHO): c.549dup (p.Gln184fs) duplication Pathogenic 3:129251112-129251112 3:129532269-129532269
4 MPZ NM_000530.8(MPZ): c.637G> A (p.Gly213Arg) single nucleotide variant Uncertain significance 1:161275906-161275906 1:161306116-161306116

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Congenital Hypomyelinating, 2:

74
# Symbol AA change Variation ID SNP ID
1 MPZ p.Thr124Lys VAR_029978 rs121913595

Expression for Neuropathy, Congenital Hypomyelinating, 2

Search GEO for disease gene expression data for Neuropathy, Congenital Hypomyelinating, 2.

Pathways for Neuropathy, Congenital Hypomyelinating, 2

GO Terms for Neuropathy, Congenital Hypomyelinating, 2

Cellular components related to Neuropathy, Congenital Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 8.62 RHO MPZ

Sources for Neuropathy, Congenital Hypomyelinating, 2

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10 dbSNP
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54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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