HMSN6A
MCID: NRP059
MIFTS: 34

Neuropathy, Hereditary Motor and Sensory, Type Via (HMSN6A)

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

Aliases & Classifications for Neuropathy, Hereditary Motor and Sensory, Type Via

MalaCards integrated aliases for Neuropathy, Hereditary Motor and Sensory, Type Via:

Name: Neuropathy, Hereditary Motor and Sensory, Type Via 58
Peripheral Neuropathy and Optic Atrophy 58 60 76
Charcot-Marie-Tooth Disease Type 6 12 60 15
Hmsn Vi 60 76 56
Cmt6 58 60 76
Hereditary Motor and Sensory Neuropathy Type Vi 60 76
Hereditary Motor and Sensory Neuropathy Type 6 12 60
Hmsn Via 58 76
Hmsn6a 58 76
Hmsn6 58 76
Cmt6a 58 76
Hereditary Motor and Sensory Neuropathy with Optic Atrophy 74
Neuropathy, Hereditary Motor and Sensory, Type Vi; Hmsn6 58
Neuropathy, Hereditary Motor and Sensory, Type Vi 58
Hereditary Motor and Sensory Neuropathy Type Via 76
Neuropathy, Hereditary Motor and Sensory, 6a 76
Charcot-Marie-Tooth Disease, Type 6a; Cmt6a 58
Hereditary Motor and Sensory Neuropathy Via 58
Hereditary Motor and Sensory Neuropathy Vi 13
Charcot-Marie-Tooth Disease, Type 6; Cmt6 58
Charcot-Marie-Tooth Disease, Type 6a 58
Charcot-Marie-Tooth Disease, Type 6 58
Charcot-Marie-Tooth Disease 6a 76
Charcot-Marie-Tooth Disease 6 76
Hmsn 6 60

Characteristics:

Orphanet epidemiological data:

60
hereditary motor and sensory neuropathy type 6
Inheritance: Autosomal dominant;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
early onset of peripheral neuropathy (mean 2.1 years, range 1 to 10 years)
later onset of optic atrophy (mean 19 years, range 5 to 50 years)
incomplete penetrance of optic atrophy
allelic disorder to charcot-marie-tooth disease type 2a2 (cmt2a2, )
autosomal recessive inheritance has also been reported


HPO:

33
neuropathy, hereditary motor and sensory, type via:
Onset and clinical course infantile onset
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Neuropathy, Hereditary Motor and Sensory, Type Via

UniProtKB/Swiss-Prot : 76 Neuropathy, hereditary motor and sensory, 6A: An autosomal dominant neurologic disorder characterized by optic atrophy and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities.

MalaCards based summary : Neuropathy, Hereditary Motor and Sensory, Type Via, also known as peripheral neuropathy and optic atrophy, is related to neuropathy and 3-methylglutaconic aciduria, type iii. An important gene associated with Neuropathy, Hereditary Motor and Sensory, Type Via is MFN2 (Mitofusin 2). Affiliated tissues include eye and brain, and related phenotypes are mild neurosensory hearing impairment and scoliosis

Disease Ontology : 12 A Charcot-Marie-Tooth disease that is characterized by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity.

OMIM : 58 Hereditary motor and sensory neuropathy type VI is an autosomal dominant neurologic disorder characterized by peripheral neuropathy and optic atrophy (summary by Voo et al., 2003). (601152)

Related Diseases for Neuropathy, Hereditary Motor and Sensory, Type Via

Graphical network of the top 20 diseases related to Neuropathy, Hereditary Motor and Sensory, Type Via:



Diseases related to Neuropathy, Hereditary Motor and Sensory, Type Via

Symptoms & Phenotypes for Neuropathy, Hereditary Motor and Sensory, Type Via

Human phenotypes related to Neuropathy, Hereditary Motor and Sensory, Type Via:

33 (show all 26)
# Description HPO Frequency HPO Source Accession
1 mild neurosensory hearing impairment 33 occasional (7.5%) HP:0008587
2 scoliosis 33 HP:0002650
3 optic atrophy 33 HP:0000648
4 abnormality of visual evoked potentials 33 HP:0000649
5 pes cavus 33 HP:0001761
6 decreased motor nerve conduction velocity 33 HP:0003431
7 areflexia 33 HP:0001284
8 central scotoma 33 HP:0000603
9 hyporeflexia 33 HP:0001265
10 slow decrease in visual acuity 33 HP:0007924
11 optic disc pallor 33 HP:0000543
12 proximal muscle weakness 33 HP:0003701
13 tinnitus 33 HP:0000360
14 limb muscle weakness 33 HP:0003690
15 anosmia 33 HP:0000458
16 distal muscle weakness 33 HP:0002460
17 steppage gait 33 HP:0003376
18 vocal cord paresis 33 HP:0001604
19 lumbar hyperlordosis 33 HP:0002938
20 distal amyotrophy 33 HP:0003693
21 distal sensory impairment 33 HP:0002936
22 dysmetric saccades 33 HP:0000641
23 distal sensory impairment of all modalities 33 HP:0003409
24 positive romberg sign 33 HP:0002403
25 axonal degeneration/regeneration 33 HP:0003378
26 color vision defect 33 HP:0000551

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
optic atrophy
central scotoma
dysmetric saccades
pale optic disks
subacute deterioration of visual acuity
more
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
proximal muscle weakness
distal sensory impairment of all modalities
positive romberg sign
more
Head And Neck Ears:
hearing loss, mild (rare)
tinnitus (rare)

Respiratory Larynx:
vocal cord paresis in severe cases

Skeletal Feet:
pes cavus

Skeletal Spine:
lumbar hyperlordosis
scoliosis in severe cases

Head And Neck Nose:
anosmia (rare)

Clinical features from OMIM:

601152

Drugs & Therapeutics for Neuropathy, Hereditary Motor and Sensory, Type Via

Search Clinical Trials , NIH Clinical Center for Neuropathy, Hereditary Motor and Sensory, Type Via

Genetic Tests for Neuropathy, Hereditary Motor and Sensory, Type Via

Anatomical Context for Neuropathy, Hereditary Motor and Sensory, Type Via

MalaCards organs/tissues related to Neuropathy, Hereditary Motor and Sensory, Type Via:

42
Eye, Brain

Publications for Neuropathy, Hereditary Motor and Sensory, Type Via

Articles related to Neuropathy, Hereditary Motor and Sensory, Type Via:

# Title Authors Year
1
X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene. ( 26801680 )
2016
2
Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction. ( 18946002 )
2008
3
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. ( 16437557 )
2006
4
Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. ( 16835246 )
2006
5
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. ( 15064763 )
2004

Variations for Neuropathy, Hereditary Motor and Sensory, Type Via

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Hereditary Motor and Sensory, Type Via:

76
# Symbol AA change Variation ID SNP ID
1 MFN2 p.Arg94Gln VAR_018609 rs28940291
2 MFN2 p.Arg94Trp VAR_029876 rs119103263
3 MFN2 p.Thr206Ile VAR_029877 rs119103266
4 MFN2 p.Gln276Arg VAR_029878 rs119103264
5 MFN2 p.His361Tyr VAR_029879
6 MFN2 p.Arg364Trp VAR_029880 rs119103265

ClinVar genetic disease variations for Neuropathy, Hereditary Motor and Sensory, Type Via:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 MFN2 NM_014874.3(MFN2): c.2219G> C (p.Trp740Ser) single nucleotide variant Pathogenic rs28940292 GRCh37 Chromosome 1, 12071567: 12071567
2 MFN2 NM_014874.3(MFN2): c.2219G> C (p.Trp740Ser) single nucleotide variant Pathogenic rs28940292 GRCh38 Chromosome 1, 12011510: 12011510
3 MFN2 NM_014874.3(MFN2): c.280C> T (p.Arg94Trp) single nucleotide variant Pathogenic rs119103263 GRCh37 Chromosome 1, 12052716: 12052716
4 MFN2 NM_014874.3(MFN2): c.2119C> T (p.Arg707Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119103267 GRCh38 Chromosome 1, 12009641: 12009641
5 MFN2 NM_014874.3(MFN2): c.280C> T (p.Arg94Trp) single nucleotide variant Pathogenic rs119103263 GRCh38 Chromosome 1, 11992659: 11992659
6 MFN2 NM_014874.3(MFN2): c.827A> G (p.Gln276Arg) single nucleotide variant Pathogenic rs119103264 GRCh37 Chromosome 1, 12061468: 12061468
7 MFN2 NM_014874.3(MFN2): c.827A> G (p.Gln276Arg) single nucleotide variant Pathogenic rs119103264 GRCh38 Chromosome 1, 12001411: 12001411
8 MFN2 NM_014874.3(MFN2): c.1090C> T (p.Arg364Trp) single nucleotide variant Pathogenic rs119103265 GRCh37 Chromosome 1, 12062090: 12062090
9 MFN2 NM_014874.3(MFN2): c.1090C> T (p.Arg364Trp) single nucleotide variant Pathogenic rs119103265 GRCh38 Chromosome 1, 12002033: 12002033
10 MFN2 NM_014874.3(MFN2): c.617C> T (p.Thr206Ile) single nucleotide variant Pathogenic rs119103266 GRCh37 Chromosome 1, 12058844: 12058844
11 MFN2 NM_014874.3(MFN2): c.617C> T (p.Thr206Ile) single nucleotide variant Pathogenic rs119103266 GRCh38 Chromosome 1, 11998787: 11998787
12 MFN2 NM_014874.3(MFN2): c.2119C> T (p.Arg707Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119103267 GRCh37 Chromosome 1, 12069698: 12069698
13 MFN2 NM_014874.3(MFN2): c.310C> T (p.Arg104Trp) single nucleotide variant Pathogenic rs119103268 GRCh37 Chromosome 1, 12052746: 12052746
14 MFN2 NM_014874.3(MFN2): c.310C> T (p.Arg104Trp) single nucleotide variant Pathogenic rs119103268 GRCh38 Chromosome 1, 11992689: 11992689
15 MFN2 NM_001127660.1(MFN2): c.720C> G (p.Phe240Leu) single nucleotide variant Likely pathogenic rs864622480 GRCh37 Chromosome 1, 12059056: 12059056
16 MFN2 NM_001127660.1(MFN2): c.720C> G (p.Phe240Leu) single nucleotide variant Likely pathogenic rs864622480 GRCh38 Chromosome 1, 11998999: 11998999
17 MFN2 NM_014874.3(MFN2): c.1143_1145delGGC (p.Ala383del) deletion Uncertain significance rs1553144065 GRCh37 Chromosome 1, 12062143: 12062145
18 MFN2 NM_014874.3(MFN2): c.1143_1145delGGC (p.Ala383del) deletion Uncertain significance rs1553144065 GRCh38 Chromosome 1, 12002086: 12002088
19 MFN2 NM_014874.3(MFN2): c.1837_1838insG (p.Thr614Aspfs) insertion Likely pathogenic rs1553145402 GRCh37 Chromosome 1, 12066716: 12066716
20 MFN2 NM_014874.3(MFN2): c.1837_1838insG (p.Thr614Aspfs) insertion Likely pathogenic rs1553145402 GRCh38 Chromosome 1, 12006658: 12006659

Expression for Neuropathy, Hereditary Motor and Sensory, Type Via

Search GEO for disease gene expression data for Neuropathy, Hereditary Motor and Sensory, Type Via.

Pathways for Neuropathy, Hereditary Motor and Sensory, Type Via

GO Terms for Neuropathy, Hereditary Motor and Sensory, Type Via

Cellular components related to Neuropathy, Hereditary Motor and Sensory, Type Via according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.13 C12orf65 MFN2 SLC25A46
2 mitochondrial outer membrane GO:0005741 8.62 MFN2 SLC25A46

Sources for Neuropathy, Hereditary Motor and Sensory, Type Via

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70 SNOMED-CT via HPO
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