CHN2
MCID: NRP064
MIFTS: 35

Neuropathy, Congenital Hypomyelinating, 2 (CHN2)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Neuropathy, Congenital Hypomyelinating, 2

MalaCards integrated aliases for Neuropathy, Congenital Hypomyelinating, 2:

Name: Neuropathy, Congenital Hypomyelinating, 2 57 72
Hypomyelinating Neuropathy, Congenital, 2 57 72
Congenital Hypomyelinating Neuropathy 2 29 6
Chn2 57 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
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® : 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) (Updated 20-May-2021)

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 skeletal muscle, cortex and kidney, and related phenotypes are scoliosis and skeletal muscle atrophy

UniProtKB/Swiss-Prot : 72 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

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 skeletal muscle atrophy 31 HP:0003202
3 respiratory insufficiency due to muscle weakness 31 HP:0002747
4 areflexia 31 HP:0001284
5 decreased fetal movement 31 HP:0001558
6 hyporeflexia 31 HP:0001265
7 decreased motor nerve conduction velocity 31 HP:0003431
8 severe muscular hypotonia 31 HP:0006829
9 poor head control 31 HP:0002421
10 inability to walk 31 HP:0002540
11 hypokinesia 31 HP:0002375
12 facial diplegia 31 HP:0001349
13 delayed ability to walk 31 HP:0031936
14 abnormal foot morphology 31 HP:0001760

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

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
Skeletal Muscle, Cortex, Kidney, Colon, Thyroid, Ovary, Myeloid

Publications for Neuropathy, Congenital Hypomyelinating, 2

Articles related to Neuropathy, Congenital Hypomyelinating, 2:

(show top 50) (show all 163)
# Title Authors PMID Year
1
Congenital hypomyelinating neuropathy, a long term follow-up study in an affected family. 6 57
17825553 2008
2
A novel MPZ gene mutation in congenital neuropathy with hypomyelination. 57 6
15184631 2004
3
Disturbance of muscle fiber differentiation in congenital hypomyelinating neuropathy caused by a novel myelin protein zero mutation. 57 6
12953275 2003
4
Congenital hypomyelination due to myelin protein zero Q215X mutation. 6 57
10319895 1999
5
Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. 6 57
8816708 1996
6
Variability in the Viral Protein Linked to the Genome of Turnip Mosaic Virus Influences Interactions with eIF(iso)4Es in Brassica rapa. 61
33551696 2021
7
Efficacy and Safety of Once Weekly Dulaglutide in East Asian Patients with Type 2 Diabetes: Subgroup Analysis by Potential Influential Factors. 61
33161492 2021
8
Efficacy and Safety of Once-Weekly Dulaglutide in Elderly Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN Studies. 61
32857293 2020
9
Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. 61
32707573 2020
10
Evaluation of Characteristics of Gastrointestinal Adverse Events with Once-Weekly Dulaglutide Treatment in Chinese Patients with Type 2 Diabetes: A Post Hoc Pooled Analysis of Two Randomized Trials. 61
32621083 2020
11
SOX10-regulated promoter use defines isoform-specific gene expression in Schwann cells. 61
32770939 2020
12
Efficacy and Safety of Dulaglutide by Baseline HbA1c in Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis. 61
32277401 2020
13
A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals. 61
32511357 2020
14
Identification of a truncated β1-chimaerin variant that inactivates nuclear Rac1. 61
31871052 2020
15
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
16
Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants. 61
31594917 2019
17
Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2). 61
31228090 2019
18
CHN2 Promoter Methylation Change May Be Associated With Methamphetamine Dependence. 61
29719347 2017
19
Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex. 61
26874185 2017
20
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
21
Multi-electron redox processes at a Zr(iv) center facilitated by an appended redox-active cobalt-containing metalloligand. 61
27326824 2016
22
The synthesis, structure and reactivity of an imine-stabilized carboranylphosphorus(i) compound. 61
27180610 2016
23
Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans. 61
27448167 2016
24
Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy. 61
26248552 2015
25
Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility. 61
26315110 2015
26
High-Resolution Array Comparative Genomic Hybridization Utility in Polish Newborns with Isolated Cleft Lip and Palate. 61
25613075 2015
27
Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients. 61
24854763 2014
28
Genome characterization of sugarcane yellow leaf virus from China reveals a novel recombinant genotype. 61
24395076 2014
29
Generation of C(2)F(5)CHN(2) in situ and its first reaction: [3+2] cycloaddition with alkenes. 61
24700600 2014
30
Influence of model grid resolution on NO2 vertical column densities over East Asia. 61
24843914 2014
31
Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study. 61
24725463 2014
32
Genome-wide association and pharmacological profiling of 29 anticancer agents using lymphoblastoid cell lines. 61
24444404 2014
33
Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. 61
25057852 2014
34
β3-chimaerin, a novel member of the chimaerin Rac-GAP family. 61
24430297 2014
35
Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease. 61
24551085 2014
36
Association of a novel polymorphism of the β2-chimaerin gene (CHN2) with smoking. 61
23941981 2013
37
Genome-wide association study of atypical psychosis. 61
24132900 2013
38
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
39
Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling. 61
23572233 2013
40
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. 61
22210626 2012
41
CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients. 61
21911749 2011
42
Genetic associations in diabetic nephropathy: a meta-analysis. 61
21127830 2011
43
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
44
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
45
Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini. 61
18092178 2008
46
Comparison of cysteine peptidase activities in Trichobilharzia regenti and Schistosoma mansoni cercariae. 61
17517170 2007
47
The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. 61
17020538 2007
48
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
49
Labelling of four distinct trophozoite falcipains of Plasmodium falciparum by a cystatin-derived probe. 61
15899703 2005
50
Characterization of human ARHGAP10 gene in silico. 61
15375573 2004

Variations for Neuropathy, Congenital Hypomyelinating, 2

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

6 (show all 35)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MPZ NM_000530.8(MPZ):c.643C>T (p.Gln215Ter) SNV Pathogenic 14178 rs121913593 GRCh37: 1:161275900-161275900
GRCh38: 1:161306110-161306110
2 MPZ MPZ, 3-BP DEL/1-BP INS, NT550 Indel Pathogenic 14192 GRCh37:
GRCh38:
3 MPZ NM_000530.8(MPZ):c.371C>A (p.Thr124Lys) SNV Pathogenic 14196 rs121913595 GRCh37: 1:161276575-161276575
GRCh38: 1:161306785-161306785
4 RHO NM_000539.3(RHO):c.549dup (p.Gln184fs) Duplication Pathogenic 590911 rs1560046845 GRCh37: 3:129251111-129251112
GRCh38: 3:129532268-129532269
5 MPZ NM_000530.8(MPZ):c.637G>A (p.Gly213Arg) SNV Uncertain significance 638456 rs202176679 GRCh37: 1:161275906-161275906
GRCh38: 1:161306116-161306116
6 MPZ NM_000530.8(MPZ):c.*52G>A SNV Uncertain significance 293311 rs774701563 GRCh37: 1:161275614-161275614
GRCh38: 1:161305824-161305824
7 MPZ NM_000530.8(MPZ):c.77C>T (p.Pro26Leu) SNV Uncertain significance 293314 rs530923760 GRCh37: 1:161277205-161277205
GRCh38: 1:161307415-161307415
8 MPZ NM_000530.8(MPZ):c.*954C>A SNV Uncertain significance 293301 rs372340608 GRCh37: 1:161274712-161274712
GRCh38: 1:161304922-161304922
9 MPZ NM_000530.8(MPZ):c.*1074A>C SNV Uncertain significance 293298 rs886045471 GRCh37: 1:161274592-161274592
GRCh38: 1:161304802-161304802
10 MPZ NM_000530.8(MPZ):c.*743C>T SNV Uncertain significance 293305 rs140992541 GRCh37: 1:161274923-161274923
GRCh38: 1:161305133-161305133
11 MPZ NM_000530.8(MPZ):c.*681A>T SNV Uncertain significance 293306 rs886045474 GRCh37: 1:161274985-161274985
GRCh38: 1:161305195-161305195
12 MPZ NM_000530.8(MPZ):c.*251C>G SNV Uncertain significance 293309 rs772995394 GRCh37: 1:161275415-161275415
GRCh38: 1:161305625-161305625
13 MPZ NM_000530.8(MPZ):c.*195G>T SNV Uncertain significance 293310 rs150182811 GRCh37: 1:161275471-161275471
GRCh38: 1:161305681-161305681
14 MPZ NM_000530.8(MPZ):c.*1048A>T SNV Uncertain significance 293299 rs71639057 GRCh37: 1:161274618-161274618
GRCh38: 1:161304828-161304828
15 MPZ NM_000530.8(MPZ):c.*1020G>A SNV Uncertain significance 293300 rs886045472 GRCh37: 1:161274646-161274646
GRCh38: 1:161304856-161304856
16 MPZ NM_000530.8(MPZ):c.-49C>A SNV Uncertain significance 293315 rs750777955 GRCh37: 1:161279744-161279744
GRCh38: 1:161309954-161309954
17 MPZ NM_000530.8(MPZ):c.444A>T (p.Glu148Asp) SNV Uncertain significance 873574 GRCh37: 1:161276502-161276502
GRCh38: 1:161306712-161306712
18 MPZ NM_000530.8(MPZ):c.*341A>G SNV Uncertain significance 874466 GRCh37: 1:161275325-161275325
GRCh38: 1:161305535-161305535
19 MPZ NM_000530.8(MPZ):c.*102C>T SNV Uncertain significance 874516 GRCh37: 1:161275564-161275564
GRCh38: 1:161305774-161305774
20 MPZ NM_000530.8(MPZ):c.428C>T (p.Thr143Met) SNV Uncertain significance 531684 rs750724650 GRCh37: 1:161276518-161276518
GRCh38: 1:161306728-161306728
21 MPZ NM_000530.8(MPZ):c.200G>A (p.Arg67His) SNV Uncertain significance 237875 rs201720099 GRCh37: 1:161277082-161277082
GRCh38: 1:161307292-161307292
22 MPZ NM_000530.8(MPZ):c.*522C>A SNV Uncertain significance 875383 GRCh37: 1:161275144-161275144
GRCh38: 1:161305354-161305354
23 MPZ NM_000530.8(MPZ):c.*435T>G SNV Uncertain significance 875384 GRCh37: 1:161275231-161275231
GRCh38: 1:161305441-161305441
24 MPZ NM_000530.8(MPZ):c.184A>G (p.Ile62Val) SNV Uncertain significance 875495 GRCh37: 1:161277098-161277098
GRCh38: 1:161307308-161307308
25 MPZ NM_000530.8(MPZ):c.*903G>A SNV Uncertain significance 876254 GRCh37: 1:161274763-161274763
GRCh38: 1:161304973-161304973
26 MPZ NM_000530.8(MPZ):c.*752G>A SNV Uncertain significance 876373 GRCh37: 1:161274914-161274914
GRCh38: 1:161305124-161305124
27 MPZ NM_000530.8(MPZ):c.*369C>T SNV Uncertain significance 876415 GRCh37: 1:161275297-161275297
GRCh38: 1:161305507-161305507
28 MPZ NM_000530.8(MPZ):c.*360C>G SNV Uncertain significance 876416 GRCh37: 1:161275306-161275306
GRCh38: 1:161305516-161305516
29 MPZ NM_000530.8(MPZ):c.637G>C (p.Gly213Arg) SNV Likely benign 246572 rs202176679 GRCh37: 1:161275906-161275906
GRCh38: 1:161306116-161306116
30 MPZ NM_000530.8(MPZ):c.*624C>T SNV Likely benign 293307 rs60821801 GRCh37: 1:161275042-161275042
GRCh38: 1:161305252-161305252
31 MPZ NM_000530.8(MPZ):c.*568C>G SNV Likely benign 293308 rs60731755 GRCh37: 1:161275098-161275098
GRCh38: 1:161305308-161305308
32 MPZ NM_000530.8(MPZ):c.684C>T (p.Ser228=) SNV Likely benign 129619 rs34307129 GRCh37: 1:161275729-161275729
GRCh38: 1:161305939-161305939
33 MPZ NM_000530.8(MPZ):c.504G>A (p.Val168=) SNV Likely benign 293313 rs145592910 GRCh37: 1:161276199-161276199
GRCh38: 1:161306409-161306409
34 MPZ NM_000530.8(MPZ):c.*761A>G SNV Benign 293304 rs16832786 GRCh37: 1:161274905-161274905
GRCh38: 1:161305115-161305115
35 MPZ NM_000530.8(MPZ):c.600G>A (p.Gly200=) SNV Benign 138242 rs16832790 GRCh37: 1:161275943-161275943
GRCh38: 1:161306153-161306153

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

72
# 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

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