CHN2
MCID: NRP064
MIFTS: 35

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 56 73
Hypomyelinating Neuropathy, Congenital, 2 56 73
Congenital Hypomyelinating Neuropathy 2 29 6
Chn2 56 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
onset at birth or in utero


HPO:

31
neuropathy, congenital hypomyelinating, 2:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:



Summaries for Neuropathy, Congenital Hypomyelinating, 2

OMIM : 56 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 duodenum adenocarcinoma. 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 : 73 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 11.5
2 duodenum adenocarcinoma 11.2
3 hepatosplenic t-cell lymphoma 11.2
4 diabetes mellitus, noninsulin-dependent 10.2
5 severe combined immunodeficiency 10.2
6 substance dependence 10.2
7 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 9.4 RHO MPZ
8 bardet-biedl syndrome 9.2 RHO MPZ

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:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 HP:0002650
2 respiratory insufficiency due to muscle weakness 31 HP:0002747
3 skeletal muscle atrophy 31 HP:0003202
4 areflexia 31 HP:0001284
5 decreased fetal movement 31 HP:0001558
6 abnormality of the foot 31 HP:0001760
7 hyporeflexia 31 HP:0001265
8 decreased motor nerve conduction velocity 31 HP:0003431
9 severe muscular hypotonia 31 HP:0006829
10 poor head control 31 HP:0002421
11 inability to walk 31 HP:0002540
12 hypokinesia 31 HP:0002375
13 facial diplegia 31 HP:0001349
14 delayed ability to walk 31 HP:0031936

Symptoms via clinical synopsis from OMIM:

56
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:
poor head control
inability to walk
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:

40
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 157)
# Title Authors PMID Year
1
Congenital hypomyelinating neuropathy, a long term follow-up study in an affected family. 6 56
17825553 2008
2
A novel MPZ gene mutation in congenital neuropathy with hypomyelination. 56 6
15184631 2004
3
Disturbance of muscle fiber differentiation in congenital hypomyelinating neuropathy caused by a novel myelin protein zero mutation. 6 56
12953275 2003
4
Congenital hypomyelination due to myelin protein zero Q215X mutation. 56
10319895 1999
5
Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. 56
8816708 1996
6
Efficacy and Safety of Dulaglutide by Baseline HbA1c in Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis. 61
32277401 2020
7
A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals. 61
32511357 2020
8
Identification of a truncated β1-chimaerin variant that inactivates nuclear Rac1. 61
31871052 2020
9
Candidate Gene and Genome-Wide Association Studies for Circulating Leptin Levels Reveal Population and Sex-Specific Associations in High Cardiovascular Risk Mediterranean Subjects. 61
31766143 2019
10
Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants. 61
31594917 2019
11
Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2). 61
31228090 2019
12
CHN2 Promoter Methylation Change May Be Associated With Methamphetamine Dependence. 61
29719347 2017
13
Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex. 61
26874185 2017
14
Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity. 61
28068899 2017
15
Multi-electron redox processes at a Zr(iv) center facilitated by an appended redox-active cobalt-containing metalloligand. 61
27326824 2016
16
The synthesis, structure and reactivity of an imine-stabilized carboranylphosphorus(i) compound. 61
27180610 2016
17
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. 61
27448167 2016
18
Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy. 61
26248552 2015
19
Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility. 61
26315110 2015
20
High-Resolution Array Comparative Genomic Hybridization Utility in Polish Newborns with Isolated Cleft Lip and Palate. 61
25613075 2015
21
Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients. 61
24854763 2014
22
Genome characterization of sugarcane yellow leaf virus from China reveals a novel recombinant genotype. 61
24395076 2014
23
Influence of model grid resolution on NO2 vertical column densities over East Asia. 61
24843914 2014
24
Generation of C(2)F(5)CHN(2) in situ and its first reaction: [3+2] cycloaddition with alkenes. 61
24700600 2014
25
Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study. 61
24725463 2014
26
Genome-wide association and pharmacological profiling of 29 anticancer agents using lymphoblastoid cell lines. 61
24444404 2014
27
Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease. 61
24551085 2014
28
β3-chimaerin, a novel member of the chimaerin Rac-GAP family. 61
24430297 2014
29
Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. 61
25057852 2014
30
Genome-wide association study of atypical psychosis. 61
24132900 2013
31
Association of a novel polymorphism of the β2-chimaerin gene (CHN2) with smoking. 61
23941981 2013
32
Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation. 61
23747354 2013
33
Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling. 61
23572233 2013
34
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. 61
22210626 2012
35
CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients. 61
21911749 2011
36
Genetic associations in diabetic nephropathy: a meta-analysis. 61
21127830 2011
37
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. 61
20460425 2010
38
Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism. 61
19720790 2009
39
Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini. 61
18092178 2008
40
Comparison of cysteine peptidase activities in Trichobilharzia regenti and Schistosoma mansoni cercariae. 61
17517170 2007
41
The cysteine proteinase inhibitor Z-Phe-Ala-CHN2 alters cell morphology and cell division activity of Trypanosoma brucei bloodstream forms in vivo. 61
17328798 2007
42
The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. 61
17020538 2007
43
Labelling of four distinct trophozoite falcipains of Plasmodium falciparum by a cystatin-derived probe. 61
15899703 2005
44
Characterization of human ARHGAP10 gene in silico. 61
15375573 2004
45
Osteoclastogenesis is decreased by cysteine proteinase inhibitors. 61
15003789 2004
46
Molecular and enzymatic properties of a cathepsin L-like proteinase with distinct substrate specificity from northern shrimp (Pandalus borealis). 61
14574613 2004
47
Microarray analysis of gene-expression profiles in diffuse large B-cell lymphoma: identification of genes related to disease progression. 61
12716467 2002
48
Peptidyl diazomethyl ketones inhibit the human rhinovirus 3C protease: effect on virus yield by partial block of P3 polyprotein processing. 61
11900346 2001
49
Dipeptide vinyl sulfones suitable for intracellular inhibition of dipeptidyl peptidase I. 61
11367515 2001
50
Altered expression of cruzipain and a cathepsin B-like target in a Trypanosoma cruzi cell line displaying resistance to synthetic inhibitors of cysteine-proteinases. 61
10924756 2000

Variations for Neuropathy, Congenital Hypomyelinating, 2

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

6 (show all 34) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RHO NM_000539.3(RHO):c.549dup (p.Gln184fs)duplication Pathogenic 590911 rs1560046845 3:129251111-129251112 3:129532268-129532269
2 MPZ MPZ, 3-BP DEL/1-BP INS, NT550indel Pathogenic 14192
3 MPZ NM_000530.8(MPZ):c.371C>A (p.Thr124Lys)SNV Pathogenic 14196 rs121913595 1:161276575-161276575 1:161306785-161306785
4 MPZ NM_000530.8(MPZ):c.200G>A (p.Arg67His)SNV Conflicting interpretations of pathogenicity 237875 rs201720099 1:161277082-161277082 1:161307292-161307292
5 MPZ NM_000530.8(MPZ):c.637G>C (p.Gly213Arg)SNV Conflicting interpretations of pathogenicity 246572 rs202176679 1:161275906-161275906 1:161306116-161306116
6 MPZ NM_000530.8(MPZ):c.*360C>GSNV Conflicting interpretations of pathogenicity 876416 1:161275306-161275306 1:161305516-161305516
7 MPZ NM_000530.8(MPZ):c.-49C>ASNV Conflicting interpretations of pathogenicity 293315 rs750777955 1:161279744-161279744 1:161309954-161309954
8 MPZ NM_000530.8(MPZ):c.*52G>ASNV Conflicting interpretations of pathogenicity 293311 rs774701563 1:161275614-161275614 1:161305824-161305824
9 MPZ NM_000530.8(MPZ):c.*743C>TSNV Conflicting interpretations of pathogenicity 293305 rs140992541 1:161274923-161274923 1:161305133-161305133
10 MPZ NM_000530.8(MPZ):c.*195G>TSNV Conflicting interpretations of pathogenicity 293310 rs150182811 1:161275471-161275471 1:161305681-161305681
11 MPZ NM_000530.8(MPZ):c.*1048A>TSNV Conflicting interpretations of pathogenicity 293299 rs71639057 1:161274618-161274618 1:161304828-161304828
12 MPZ NM_000530.8(MPZ):c.77C>T (p.Pro26Leu)SNV Conflicting interpretations of pathogenicity 293314 rs530923760 1:161277205-161277205 1:161307415-161307415
13 MPZ NM_000530.8(MPZ):c.428C>T (p.Thr143Met)SNV Uncertain significance 531684 rs750724650 1:161276518-161276518 1:161306728-161306728
14 MPZ NM_000530.8(MPZ):c.*1074A>CSNV Uncertain significance 293298 rs886045471 1:161274592-161274592 1:161304802-161304802
15 MPZ NM_000530.8(MPZ):c.*251C>GSNV Uncertain significance 293309 rs772995394 1:161275415-161275415 1:161305625-161305625
16 MPZ NM_000530.8(MPZ):c.*1020G>ASNV Uncertain significance 293300 rs886045472 1:161274646-161274646 1:161304856-161304856
17 MPZ NM_000530.8(MPZ):c.*954C>ASNV Uncertain significance 293301 rs372340608 1:161274712-161274712 1:161304922-161304922
18 MPZ NM_000530.8(MPZ):c.*341A>GSNV Uncertain significance 874466 1:161275325-161275325 1:161305535-161305535
19 MPZ NM_000530.8(MPZ):c.*102C>TSNV Uncertain significance 874516 1:161275564-161275564 1:161305774-161305774
20 MPZ NM_000530.8(MPZ):c.444A>T (p.Glu148Asp)SNV Uncertain significance 873574 1:161276502-161276502 1:161306712-161306712
21 MPZ NM_000530.8(MPZ):c.184A>G (p.Ile62Val)SNV Uncertain significance 875495 1:161277098-161277098 1:161307308-161307308
22 MPZ NM_000530.8(MPZ):c.637G>A (p.Gly213Arg)SNV Uncertain significance 638456 1:161275906-161275906 1:161306116-161306116
23 MPZ NM_000530.8(MPZ):c.*903G>ASNV Uncertain significance 876254 1:161274763-161274763 1:161304973-161304973
24 MPZ NM_000530.8(MPZ):c.*752G>ASNV Uncertain significance 876373 1:161274914-161274914 1:161305124-161305124
25 MPZ NM_000530.8(MPZ):c.*522C>ASNV Uncertain significance 875383 1:161275144-161275144 1:161305354-161305354
26 MPZ NM_000530.8(MPZ):c.*435T>GSNV Uncertain significance 875384 1:161275231-161275231 1:161305441-161305441
27 MPZ NM_000530.8(MPZ):c.*369C>TSNV Uncertain significance 876415 1:161275297-161275297 1:161305507-161305507
28 MPZ NM_000530.8(MPZ):c.*681A>TSNV Uncertain significance 293306 rs886045474 1:161274985-161274985 1:161305195-161305195
29 MPZ NM_000530.8(MPZ):c.*568C>GSNV Benign/Likely benign 293308 rs60731755 1:161275098-161275098 1:161305308-161305308
30 MPZ NM_000530.8(MPZ):c.684C>T (p.Ser228=)SNV Benign/Likely benign 129619 rs34307129 1:161275729-161275729 1:161305939-161305939
31 MPZ NM_000530.8(MPZ):c.504G>A (p.Val168=)SNV Benign/Likely benign 293313 rs145592910 1:161276199-161276199 1:161306409-161306409
32 MPZ NM_000530.8(MPZ):c.*624C>TSNV Benign/Likely benign 293307 rs60821801 1:161275042-161275042 1:161305252-161305252
33 MPZ NM_000530.8(MPZ):c.*761A>GSNV Benign 293304 rs16832786 1:161274905-161274905 1:161305115-161305115
34 MPZ NM_000530.8(MPZ):c.600G>A (p.Gly200=)SNV Benign 138242 rs16832790 1:161275943-161275943 1:161306153-161306153

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

73
# 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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57 OMIM via Orphanet
61 PubMed
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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